Descriptions are available - Clinical and Translational Sciences

advertisement
SF424 (R&R) Application Guide for NIH and Other PHS agencies
Other Project Information: Facilities & Other Resources
This information is used to assess the capability of the organizational resources available to perform
the effort proposed. Identify the facilities to be used (Laboratory, Animal, Computer, Office, Clinical and
Other). If appropriate, indicate their capacities, pertinent capabilities, relative proximity and extent of
availability to the project. Describe only those resources that are directly applicable to the proposed
work. Provide any information describing the Other Resources available to the project (e.g., machine
shop, electronic shop) and the extent to which they would be available to the project. Source: PHS SF
424 (R&R) Forms Version C Application Guide
MSU- General Information
The nation’s pioneer land-grant university, Michigan State University (MSU) is recognized internationally as a
top research university. Located in East Lansing, MSU encompasses a 5,200-acre campus with 2,100 acres in
existing or planned development, 538 buildings, including 95 academic buildings. These, as well eight medical
campuses distributed throughout the state are supported by over 5,100 faculty and academic staff, with
>38,000 undergraduates, and >11, 000 graduate and professional students enrolled in the 17 degree-granting
colleges at MSU.
MSU is listed among the top 50 universities in the world based on research performance, including publications
and citations based on rankings compiled at the University of Western Australia. Michigan State’s global
standing as a top-notch research and teaching institution continues to improve. The World University Rankings
by Times Higher Education, a London-based publication ranks MSU 82, up one spot from last year. Michigan
State University is among the top 100 universities in the world, according to a new set of rankings from U.S.
News & World Report. According to the rankings, which list the top 500 universities in the world, MSU is tied
for 75th with the Netherlands’ Leiden University. This is the first time U.S. News & World Report has rated
universities on a global scale. It used a new set of criteria, with a heavy emphasis on the schools’ research
prowess. For example, The Institute for Scientific Information included 27 MSU faculty members on its most
recent list of "Highly Cited" researchers. Individuals on the list are among the top 250 researchers worldwide in
their respective fields in terms of the number of citations to research published and represent about half of 1
percent of all researchers in the sciences and social sciences.
Funding for externally sponsored programs comes primarily from federal agencies, state agencies, industry
associations and foundations, with ~$528 million in external funding in 2013-14. As a result, MSU is a member
of the prestigious Association of American Universities, a group of only 60 U.S. and two Canadian universities
widely regarded as among the top research-intensive institutions in North America.
MSU is the only university in the country with on-campus medical schools graduating allopathic (MD) and
osteopathic (DO) physicians, as well as veterinarians (DVM), that each also produce dual- degreed, PhD
graduates as well. The College of Nursing is also one of the top research Nursing Colleges in the country.
Significant research infrastructure exists to support the research and training efforts underway within each of
these colleges.
Basic and T0 level research has been foundational to the successes of the 4 health and medical colleges as
they jointly benefit by sharing several distinguished basic sciences departments and their research faculty.
These include research faculty in the departments of Physiology, Biochemistry & Molecular Biology,
Microbiology and Molecular Genetics, Pharmacology and Toxicology, as well as Epidemiology and others,
each again shared with other Colleges including Engineering (COE), the College of Natural Sciences (CNS),
and the College of Agriculture and Natural Resources (CANR).
As but one example of several, the College of Natural Science at Michigan State University is home to 27
departments and programs in the biological, physical and mathematical sciences. The college averages $28 M
in research expenditures annually while providing world-class educational opportunities to more than 5,000
undergraduate majors and nearly 1,000 graduate students.
MSU- Community Setting:
The concept of “clinical and translational science” implies that extensive interaction with communities will take
place for its implementation. The Agricultural College of the State of Michigan, precursor of Michigan State
University, was chartered in 1855 as the nation’s first land-grant institution of higher education. The outreach
mission of the University was expanded by the Hatch and Smith-Lever Acts creating a series of Agricultural
Experiment Stations and the Cooperative Extension Service, with missions of Outreach and Service to the
residents of Michigan. Implementation of this mission at MSU led to establishment of the MSU Extension
Service (MSUE) with branches in all of the 83 Counties of Michigan.
For 45 years, MSU, through its distributed Health Campuses, has been educating medical students and nurses
in the communities of the State of Michigan. MSU’s three human health sciences colleges (Human Medicine,
Osteopathic Medicine and Nursing) have an education system where students begin study in East Lansing or
Grand Rapids and move to community health campuses to complete clinical training. Over 50% of the
graduates from these colleges remain in the state for postgraduate training and clinical practice, often in
primary care, many in underserved regions of the state. These and other strengths, including over 5,000
clinical faculty statewide, have established MSU as a national leader in community-based medical education.
MSU recognized early the opportunity to build on its dual foundations namely the MSUE and the three human
health sciences colleges, and in 2008 created the MSU Clinical and Translational Sciences Institute (MSUCTSI).
Community Reach and Population Diversity: MSU’s four health sciences colleges are intimately connected
with urban and rural populations of Michigan, as well as with professionals delivering health care to these
communities. MSU-CTSI will employ MSU’s existing teaching and hospital networks (Table 1) in the statewide
Zones of Research Engagement to implement its clinical and translational science mission (Grand Rapids,
Flint, Midland, Detroit area, Lansing, Traverse City region, and Marquette region). The population potentially
impacted by MSU-CTSI includes approximately 4.7 million people and is quite diverse, as noted in Table 2.
Clinical and Translational Sciences Institute (MSU-CTSI)
In August 2008, the Michigan State University established the Clinical and Translational Sciences Institute
(MSU-CTSI), recruited a Director for the Institute, consolidated existing infrastructure resources, and invested
new funds to support the CTSI mission. The MSU Office of Clinical Research (OCR) and the Biomedical
Research Informatics Core (BRIC), two independently reporting units, became divisions within the CTSI at that
time. MSU-CTSI is strongly linked to the leadership of MSU, and its Colleges and its external partners. The
goal of the MSU-CTSI is to develop clinical and translational research infrastructure to the benefit of the
communities and investigators in the MSU partner network, and ideally to expand this network by linking with
CTSA recipients across the nation. All MSU faculty members or members of partner institutions involved in
clinical and translational research and/or teaching may participate in and derive support from the MSU-CTSI.
Faculty members and other participants retain their departmental and college affiliations, but the MSU-CTSI
adds sustainability and organization to the interdisciplinary and collaborative nature and relevance of clinical
and translational research.
MSU-CTSI serves as the multi-disciplinary infrastructure to support MSU clinical and translational research.
CTSI is directed by Dr. Andrea Amalfitano, DO, Ph.D, Osteopathic Heritage Foundation Professor, who took
on this role in August of 2013. His background in medical practice, genetics research, and clinical research has
provided new expertise into an already diverse group. The Director of MSU-CTSI reports directly to the Office
of Dr. Stephen Hsu, the Vice President for Research and Graduate Studies, (OVPRGS) who reports directly to
the President’s office of MSU, Dr. Lou Anna K. Simon. MSU-CTSI is supported by general fund dollars
through the OVPRGS. Investigators engage the support of MSU-CTSI from numerous origins including the
human health colleges, basic biomedical disciplines, the social sciences, the College of Veterinary Medicine,
and the community.
MSU-CTSI and the divisions of OCR and BRIC are located West Fee Hall at MSU Main Campus in East
Lansing. The space accommodates approximately 40 individuals in 6,731 square feet of recently remodeled
space. The space has 4 conference rooms, 8 areas of cubicle space with 6 stations each organized on the
perimeter of an open common area, and 11 private office suites located on the perimeter of the space. In
addition Translational Research Support Facility (TRSF) space in West Fee Hall is currently available in
support of clinical research projects. Plans are underway to relocate and expand the TRSF in 2015. The
layout of the MSU-CTSI space is below.
Office of Clinical Research Division (OCR): The Office of Clinical Research was established in 2006 to
serve the need for enhanced support of clinical and translational research, and to expedite the research
administration process. OCR has as its mission to assist researchers with the development, implementation,
management, and completion of industry- and government-funded clinical research conducted through MSU
and community partners. OCR offers clinical research support services to investigators including feasibility
assessment, subject recruitment planning, clinical research coordination, regulatory support, connection to
external resources, and access to the local Translational Research Support Facility (TRSF) resources. Serving
as the ‘Researcher Advocate’, OCR helps faculty and staff navigate the MSU clinical research environment
and facilitates use of tools such as ResearchMatch, StudySearch, and eagle-i. ResearchMatch is a national
web-based volunteer registry that connects people interested in participating in research, with researchers
looking for participants. StudySearch is an online tool that serves as a central repository of local research
studies that are open to enrollment through MSU. Eagle-i provides researchers access to discover needed
core laboratory services, reagents, animals, specimens, etc. that are available on campus and nationally.
OCR currently serves as the point of contact for linking investigators (both locally and in the community) to
existing MSU scientists, research support, and community network resources.
Translational Research Support Facility: The MSU-CTSI TRSF currently consists of two wellequipped outpatient exam rooms, several separate areas for interviewing and study monitoring, secured space
for record and drug storage, several blood collection areas, and a specimen processing laboratory. Exam room
equipment includes infusion chairs, ECG machines, and other various equipment needed to complete physical
examinations. The specimen processing laboratory equipment includes multiple benchtop centrifuges
(refrigerated and portable) and multiple temperature-monitored refrigerators and freezers for drug sample
storage. The TRSF and staff are a registered vaccination clinic through the Michigan Care Improvement
Registry. Plans are underway for a major expansion of space and services for 2015 to accommodate the
increased need for research-dedicated clinic space, as well as to better meet the needs of research
participants.
Biomedical Research Informatics Core Division (BRIC): BRIC was established by MSU in 2001 as part of
the University’s commitment to strengthen informatics and research IT support for clinical and translational
researchers. The unit provides pre-award consultations and assistance with data management plans and
budget, as well as post award support to investigators for a variety of data capture, data security, and study
management services. BRIC provides strong support for observational studies for both internal and external
investigators, working closely with data analysis collaborators and the investigator’s team members.
BRIC provides best-in-class informatics support of the operation and administration of the MSU-CTSI. This
includes research information databases and web sites to provide information and to foster communication
among MSU clinical and translational investigators. BRIC provides a risk-based security management system
focused on the confidentiality, availability and integrity of data. It has an active program to insure compliance
with HIPAA and other federal and state laws and regulations as they pertain to data matters. BRIC reduces
barriers to the initiation of new research projects while maintaining high standards of clinical research
informatics by providing access to scalable and affordable informatics tools for pilot or early stage research;
eliminating cost barriers to high level informatics by offering no or nominal charge licenses to new investigators
or seasoned investigators beginning internally funded new lines of research; providing training and support to
assure implementation of systems relatively trouble free; using informatics solutions to reduce technical
obstacles to research initiation. Faculty and staff of the Biomedical Informatics Core (BRIC) help ensure that
data are accessed under safe and compliant conditions.
Consortium of Academic Programs in Clinical Research (CoAPCR): MSU-CTSI and the Program in Public
Health represent MSU as a member of CoAPCR. CoAPCR is comprised of global educational institutions
offering academic credit in all areas of clinical research, regulatory affairs, and clinical data management. In
addition, a supporting membership is available to organizations that are stakeholders of students graduating
from clinical research academic programs, and to other organizations that are related to the clinical research
enterprise, dedicated to enhancing the quality and safety of the clinical research enterprise through education
and training. CoAPCR facilitates the development of high-quality educational programs encompassing all
areas of clinical research that are based in academic credit-granting institutions. CoAPcR, as a member of the
Joint Task Force for Clinical Trial Competency (JTFCTC), produced the 8 domains of the harmonized core
competencies for the clinical research professional. CoAPCR’s mission is to 1) provide a medium for
communication among educators of clinical research professionals, 2) encourage and support the
development and maintenance of academically based clinical research educational programs to meet the
needs of the clinical research community, 3) foster inter-institutional articulation among educational institutions,
clinical institutions, professional associations, and industry, 4) initiate and/or support research and studies
relating to the educational, manpower and service needs of clinical research professionals.
Institutional Partners of the MSU-CTSI:
MSU is unique among American universities by having 4 health colleges (3 human, 1 animal science school):
CHM, COM, CON, and CVM. These colleges were established with major missions to train community-based
clinicians, whose primary focus is the care of patients/animals in the communities of Michigan. For clinical
education and training, CHM, COM and CON partner with regional hospitals across Michigan. After training,
these health care professionals continue to serve in smaller cities, towns and rural underserved areas. The
basic sciences education and research at these colleges are based at MSU’s central campus in East Lansing.
CHM In addition to 4-year medical schools in East Lansing and Grand Rapids, the CHM uniquely provides
students with comprehensive training in clinical settings that most closely parallel the environment in which
many physicians practice. During the third and fourth year of the CHM program (Block III), students complete a
series of required and elective clerkships at one of MSU’s seven community-based program sites, located in
Flint, Grand Rapids, Kalamazoo, Lansing, Saginaw, Traverse City and the Upper Peninsula. Each community
program is aligned with area hospitals and outpatient facilities that join MSU in creating a rich educational
environment for students. Several sites have residency programs in various specialties, as well as fellowship
programs (cardiology, hematology/oncology, endocrinology, infectious disease),
The CHM MD/PhD programs are well-integrated training programs that combines medical training (MD) with
outstanding graduate training, leading to PhDs in areas of biomedical research (East Lansing, Grand Rapids).
Community Associate Deans for education and research live in their respective communities, but meet
regularly as a group and thus are a potential link to research conducted in each of the communities. Although
most community health campuses have research offices that assist investigators to perform and present their
research, all do not have access to needed resources, particularly statistics and bioinformatics, and few have
NIH funding or mentors.
COM was the first college of osteopathic medicine at a major university in the US, and for the 14th year, the
MSU College of Osteopathic Medicine was named as one of the nation’s top colleges for educating primary
care physicians by U.S. News & World Report’s annual rankings of the best graduate schools. MSU was the
first osteopathic school to offer the “DO/PhD” dual-degree program. COM’s Statewide Campus System
comprises 30 hospitals; education directors in each hospital communicate directly with one another several
times a year. With this leadership position, and the maturation of the Osteopathic profession, COM is actively
growing its focus and investment in clinical and translational research, a transformation that is strongly assisted
by the MSU-CTSI.
CON’s community sites serve as education sites for baccalaureate students including accelerated second
degree students, Masters of Science in nursing, Certificate programs for nurse practitioners and clinical
specialists in education, as well as a PhD in nursing. The nursing programs are consistently rank high by the
U.S. News & World Report, with online graduate nursing programs ranking # 31, up 15 spots from 2013.
Masters and baccalaureate students train in approximately 120 community sites that include hospitals,
physician offices, health departments and schools. CON tenure track faculty are research intensive with the
goal of achieving funding for community based research such as chronic health conditions and health in
families and populations. Current research funding sources include NIMH, NINR, .NCI, NHLBI, USDA,
foundations, the state of Michigan, and other agencies.
CVM provides clinical services and education on MSU’s East Lansing campus. The college has expertise in
public health, biomedical and comparative medical research, ecosystem and environmental management, and
the multiple facets that compose our complex global food system. Comparative Translational Research
between human and animal disease states provides a unique opportunity to Universities with both human and
animal health colleges. MSU is particularly well poised to excel in this area due to the highly integrated nature
of the laboratory science departments across all the health colleges, a focus on how molecular and cellular
events integrate into whole-animal function in health and disease, and several strong research foci in CVM,
including oncology, cardiology, ophthalmology, pain management, and respiratory syndromes. CVM will
contribute to the MSU-CTSI mission through its education and research programs on how molecular and
cellular events integrate into whole-animal function in health and disease, and in the use of appropriate animal
models to study human and animal disease.
In 2004, health care, research, education and business leaders in Grand Rapids, the second largest city in
Michigan, collaborated and assisted MSU’s College of Human Medicine to expand its campus to West
Michigan. The vision was to solidify the existing long-term partnership between MSU CHM and Grand Rapids
health care institutions, to establish a research enterprise, and to train a new cadre of physicians and
researchers in clinical translational science, all quite consistent with the vision of the MSU-CTSI. The office of
the Dean of MSU CHM is now located in Grand Rapids.
MSU Extension: For the past 100 years, MSUE has been continuously interactive with urban and rural
communities of Michigan in all 83 counties of the State. The activities of the MSUE offices are communitycentered, needs-focused, inclusive, accessible, and collaborative. Strategic sessions, held yearly in the
communities, ascertain the most important needs of the community, which are then used to recruit MSU
researchers to address these needs. MSU has taken the unique steps of placing tenured track and other
research faculty physically in existing sites in Michigan in the Community Based Health Initiatives Sites
(CBHRI). This is an expansion of MSUE health education programs, run by county-based educators (CER
Research Liaisons with Master’s Degrees or PhDs), as well as by MSU on-campus faculty, on: [a] nutrition,
food preparation, food safety; [b] chronic disease management; [c] early childhood development; and [d] public
health. These grass-roots, stable connections to communities across the State allow us to employ this effective
and community-engaged CBHRI network to assist the MSU-CTSI to reach into our communities to understand
their health concerns and bring these back to the MSU-CTSI and then assist in jointly designing research to
address these concerns with the communities themselves. MSUE was part of significant NIH funded projects
such as the National Children’s Study (Paneth, PI HHSN2672007 00034C and HHSN275200800007C).
Hence, the inclusion of CBHRI through MSU Extension as a central component of the MSU-CTSI represents
an opportunity to establish a model for translational research collaboration in the community that can be
replicated by other CTSA funded entities throughout the nation.
University Outreach and Engagement (UOE): MSU’s UOE creates University-Community collaborative to
bring the benefits of University knowledge to the public and to address priority issues of concern to society. To
date, these activities have not addressed clinical and translational research. UOE will assist MSU-CTSI to
reach out to Michigan’s communities and engage them in relevant clinical and translational UniversityCommunity team-based research. The Carnegie Foundation for the Advancement of Teaching selected MSU
in 2007 as one of the first universities to be designated as a “Community-Engaged University”. Additional
information about UOE is noted under the Translational Science Base, Community Engagement Resources
and Facilities.
Community-based Research Networks:
Great Lakes Research Into Practice Network (GRIN): The Great Lakes Into Practice Network (GRIN)
practice-based research network, a long-standing collaboration between MSU and University of Michigan,
combined three networks: [1] Upper Peninsula Research Network (UPRNet) (established in1988), a rural
primary care research program of MSU CHM’s Department of Family Practice, in the State’s northern
territories; [2] Michigan Research Network (MIRNet) (established in 1984) co-funded by MSU, Wayne State
University and the University of Michigan involving urban and suburban health care practices in small towns
and rural locations; and [3] Primary Care Research Network (PCRNet) (established in 1985), a joint program of
MSU’s CHM and CON, which includes family practice, internal medicine, pediatrics, obstetrics/gynecology, and
nursing. The networks merged in 2000 to form GRIN. GRIN also has a collaborative relationship with
MetroNet, a practice-based research network comprising urban practices in the Detroit area created by the
Department of Family Medicine at Wayne State University Medical School. To date, over 149 practices have
actively participated in a GRIN study. The practices are evenly distributed between large, medium and small
cities; about one-half of the physicians have an academic affiliation with MSU. The patient population served
by GRIN is comprised of 13% African-Americans, 71% white, 5% Hispanic, 3% Asian, and 6% other. In 2013,
GRIN included $13 million in funded on topics ranging from diabetes prevention and self-management (PI:
Holtrop at MSU Department of Family Medicine) and patient preferences for office visit summaries (PI: Dontje
at MSU College of Nursing).
Institute for Health Policy: The mission of the Institute for Health Policy is to improve the health care
available to Michigan residents through research, policy analysis, education and outreach, and support of
quality improvement activities. The Institute achieves its mission by an ongoing commitment to health services
research, quality improvement, and health policy. The Institute for Health Policy works closely with the
Michigan Department of Community Health, Michigan Medicaid managed care plans, professional
organizations, and community-based agencies on collaborative projects to improve health care delivery in
Michigan. IHP supports and conducts health research and analysis by MSU faculty on issues of quality of care,
access to care, health disparities, and other topics impacting Medicaid, the underserved, and other
populations; conducts health policy analyses to assist decision makers at state, local, and national levels;
provides quality improvement technical assistance and support to Michigan Medicaid managed care plans and
the Michigan Medicaid program; and offers workshops, educational seminars, and web-based education for
various audiences and participates in educational functions offered by other MSU colleges and organizations.
BIG 10 Cancer Research Consortium (BTCRC): The Big Ten cancer centers have united to transform the
conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that
leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research
Consortium is to create a unique team-research culture to drive science rapidly from ideas to treatmentchanging paradigms. Within this innovative environment, today’s research leaders collaborate with and mentor
the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer. MSU,
via the Breslin Cancer Center, is a member of the BIG-CRC, a consortium that includes several CTSA
designated hubs. Additionally, Michigan cancer patients now have greater access to new and unique clinical
trials, as a consortium of eleven hospitals and research institutes in 2014 were designated by the NCI as a
NCI- Community Oncology Research Program (NCORP). CRCWM members include MSU, VARI, the Mercy
Health-Mercy Campus, Munson Medical Center, Spectrum Health, and the West Michigan Cancer Center.
Cancer Research Consortium of West Michigan (CRCWM): Grand Rapids Clinical Oncology Program
(GRCOP) initially formed to develop community cancer patient management guidelines. In 1983 GRCOP
changed its focus to become one of the first participants in the National Cancer Institute (NCI)
Community Oncology Program (CCOP), offering national clinical trials through a community-based clinical
research program. On August 1, 2014 with the support of a National Cancer Institute Clinical Oncology
Research Program (NCORP) Grant, Grand Rapids Clinical Oncology Program and Kalamazoo Community
Clinical Oncology Program joined together to form a new program: Cancer Research Consortium of West
Michigan (CRCWM). CRCWM offers local access to and data management support for over 150 cancer
research studies. CRCWM works with local hospitals and cancer organizations to provide the highest quality
care for cancer prevention and treatment. CRCWM continues to provide access to the latest cancer research
both nationally and locally.
MSU Collaborating Hospitals:
Collaborating hospitals and institutes will work within the MSU-CTSI to provide the resources necessary for a
“distributed” clinical and translational research and training enterprise. The MSU-CTSI through the MSU Health
Colleges – has affiliation relationships with 51 hospitals across Michigan who collaborate in research and
education (see Table 1). The Spectrum Health / MSU CHM Alliance in Grand Rapids provides access to the
largest tertiary care center in West Michigan; within this Alliance, over 800 clinical studies are in progress
annually. The agreements with Sparrow Hospital in Lansing and McLaren Health Care, Inc., in Southeast
Michigan, commits the resources of the hospitals and MSU CHM, COM and CON to collaborate in both clinical
practice and research areas. In addition, Marquette General Hospital in the Upper Peninsula and key hospitals
in Flint, Saginaw and Detroit provide critical opportunities for clinical and translational research.
MSU Facilities/Institutes/Centers of Particular Interest:
The Department of Biomedical Engineering: The Department of Biomedical Engineering (BME) was
approved by the MSU Board of Trustees on Oct. 24, 2014, opening the door for collaborative health care
related research between the college and rest of campus. The effective date of unit is January 1, 2015, and the
first courses in the new department will be offered in Spring 2016. The new department will become a focal
point for technological innovations in healthcare technology applied to the medical needs identified by
physicians, nurses, and health scientists in hospital, clinic, and home settings. The department will be uniquely
positioned to bring technological innovations to the vast state-wide network of healthcare providers served by
the University. Biomedical engineers will work in concert with a variety of MSU colleges, including: Human
Medicine, Osteopathic Medicine, Nursing, Natural Science, Social Science, and Communications Arts and
Sciences. Advantages will include: leveraging expertise from diverse disciplines across campus; working
together to provide cost efficiencies; mutually advancing emerging health science discoveries; helping to
improve health care accessibility. Samples of neuro-electrical interfaces include: support neuroscience
research and therapy; imaging enhancement technologies; robotics for physician assistance; sensors to
assess the health of patients in home settings.
Bioengineering Facility: Many of the new Biomedical Engineering department's activities will be
centered in the MSU Bio Engineering Facility, currently being built on the south side of campus. The almost
$61 million project has four stories and around 130,000 square feet. Faculty members are expected to start
moving into the new structure in summer or early fall 2015. Its primary tenants will be faculty members from
MSU's colleges of Engineering, Human Medicine, and Natural Science. The construction of the Bio
Engineering Facility will provide a unique opportunity to bring together research teams from engineering and
biomedical research to promote the development of bio-engineering and engineering health sciences at
Michigan State University. These emerging research areas have significant opportunities for increased federal
research funding, as well as for technology transfer to the private sector, which can promote the development
of a transformational bio-based economy in Michigan.
Collaboration between researchers from different disciplines, ranging from chemical veneering, electrical
engineering and mechanical engineering to pharmacology, physiology and radiology, will be essential in the
development of new areas of research such as tissue engineering. The new laboratory space will provide
research capacity necessary to support new hires and funded researchers in the area, and allow collaborators
from different academic units to be co-located. Faculty from the College of Engineering, College of Human
Medicine and the College of Natural Science will be the primary occupants of the building. Additional benefits
will be realized with the placement of the Bio Engineering Facility adjacent to the Clinical Center, Life Sciences,
and Radiology buildings.
Institute for Quantitative Health Science and Engineering (IQHSE): Housed in a state-of-the-art, 130,000square-foot, four-story Biomedical Engineering facility slated for completion in the Fall of 2015, the Institute is
an inter- and multi-disciplinary research center devoted to basic and applied research at the interface of life
sciences, engineering, information science, and other physical and mathematical sciences. In a collaboration
of the Colleges of Engineering, Human Medicine, and Natural Science, and drawing on the existing research
strengths of an AAU, Tier One public research university, the Institute will serve as a magnet to attract talented
researchers and will enhance the growth potential of the University as a whole. MSU envisions a research core
of at least 20 collaborators in the Institute, recruited to the University specifically to build capacity in the areas
of: computational genomics, proteomics, and other related fields; neuroscience and imaging; and data science
related to drug discovery and complex health modeling.
Grand Rapids Biomedical Research Center: Michigan State University Board of Trustees has authorized the
MSU administration to proceed with demolition of the former Grand Rapids Press building located in downtown
Grand Rapids on property the university acquired in 2012. The building to be razed is on a site of
approximately 4.3 acres, positioned immediately west of the Michigan State University College of Human
Medicine’s Secchia Center. The budget for this project (demolition) is $3 million. Funding will be provided
through the university’s general fund and tax-exempt financing with debt repayment from a variety of sources
including the general fund. Demolition is scheduled to begin in March 2015, with final completion of demolition
by December 2015.At a future MSU Board of Trustees meeting this winter, the MSU administration plans to
recommend construction of the Grand Rapids Biomedical Research Center on a portion of this site. The
remainder of the site may be divided into parcels for future development by the university and/or private
developers. Pending approvals, the new Grand Rapids Biomedical Research Center is planned to open late
2017.
The Grand Rapids Biomedical Research Building will allow the College of Human Medicine to advance its
trajectory of NIH-funded research growth. In 2010, MSU College of Human Medicine opened the Secchia
Center, a $90 million privately-funded facility constructed specifically for medical education and not designed to
accommodate research laboratories. This was part of a long-range strategy that involved MSU partnering with
Van Andel Institute and Grand Valley State University to lease laboratory space to support new NIH-funded
researchers recruited to Grand Rapids. Through December 2014, the medical school has recruited 18 principal
investigators (PIs) and their scientific teams to West Michigan and now fully occupies all desirable laboratory
space available to MSU in Grand Rapids. Over the next two years, college anticipates recruiting another 6 to 9
additional PIs, for a total of 24 to 27 – plus their research teams. Demolition is scheduled to begin in March
2015, with final completion of demolition by December 2015. Pending approvals, the new Grand Rapids
Biomedical Research Center is planned to open late 2017, and will have 145,000 sf of research space.
Renovation of Flint Campus Medical Education and Public Health Research Facility: As a result of the
ongoing community engagement in the economically depressed city of Flint, Michigan, CHM is renovating a
new 40,000 square foot facility, dedicated to pursuing the health and societal questions being raised by the
citizens of Flint, and now being addressed by the research faculty physically placed in those locations. The
medical school’s expansion was made possible by more than $11 million in grants from the Charles Stewart
Mott Foundation and the ongoing medical education support by MSU’s hospital partners Genesys Regional
Medical Center, Hurley Medical Center and McLaren Flint. MSU’s new research and learning spaces include
shared student space, four student study rooms, six clinical skills examination rooms, the college’s Flint
campus suite, offices for the program in public health and workstations to house six public health principal
investigators and their research teams. Over the next six months, more than 20 faculty and staff from the
college are moving into the new space, with room for additional people planned.
National Superconducting Cyclotron Laboratory (NSCL): NSCL is a world-leading laboratory for rare
isotope research and nuclear science education. With support from the U.S. National Science Foundation, the
laboratory operates as a national user facility that serves more than 700 researchers from 100 institutions in 35
countries. Major contributions have been made in the fields of nuclear structure, nuclear astrophysics, heavyion reaction mechanisms, accelerator physics, beam dynamics and experimental techniques. NSCL also is the
source of innovations that improve lives. A medical cyclotron built by the laboratory in the 1980s was used to
treat cancer patients at Harper University Hospital in Detroit for more than 15 years. More recently, NSCL
technology and design concepts were used in a new, higher-powered medical cyclotron built by Varian Medical
Systems. The collaboration agreement, an example of technology transfer that returns benefits to the
university, will bring more advanced nuclear therapy to cancer patients in several countries. In mid 2009,
Michigan State University and the Department of Energy Office of Science signed a cooperative agreement to
design a build a new $550 million Facility for Rare Isotope Beams (FRIB).
Facility for Rare Isotope Beams (FRIB): The U.S. Department of Energy has selected MSU to design and
establish the Facility for Rare Isotope Beams, also known as FRIB, a facility that will advance understanding of
rare nuclear isotopes and the evolution of the cosmos as it provides research opportunities for scientists and
students from around the globe. A world leader in rare isotope research, Michigan State has been committed
to advancing accelerator-based sciences for more than 50 years. The Facility for Rare Isotope Beams (FRIB)
will be a new national user facility for nuclear science, funded by the Department of Energy Office of Science
(DOE-SC), Michigan State University (MSU), and the State of Michigan. Under construction on campus and
operated by MSU, FRIB will provide intense beams of rare isotopes (that is, short-lived nuclei not normally
found on Earth). FRIB will enable scientists to make discoveries about the properties of these rare isotopes in
order to better understand the physics of nuclei, nuclear astrophysics, fundamental interactions, and
applications for society. The FRIB resource is available to power advanced biomedical research as well.
BEACON: MSU is home to BEACON, one of five highly coveted National Science Foundation Science and
Technology Innovation Centers. The Bio/computational Evolution in Action Consortium brings together
biologists, computer scientists, and engineers to study evolution in both natural and virtual settings and apply
knowledge to real-world problems, including those affecting health. BEACON capitalizes on the existing
research facilities and equipment of its members to optimize services and experiences for all participants. We
describe below some of the institutional resources that are heavily used by BEACON members at each of our
partner institutions. In addition, all faculty members maintain their own laboratory and/or computing facilities,
which are not described here.
MSU provided a Center office complex for the establishment of BEACON Headquarters, which houses the
director, deputy director, managing director, education director, diversity director, administrative assistant,
accounts manager, and information technologist, as well as 5 shared offices for faculty, postdocs, and visiting
scholars, and desk space for up to 16 graduate students. The BEACON Center has a seminar room with
Polycom and Tandberg dedicated videoconferencing equipment, augmented by a central "bridge" at MSU
(outside BEACON). Presenters are able to speak and show slides at any of the partner schools and have them
viewed at high quality at the other universities. The Center also has a conference room that seats about 15
people with a large wall-mounted monitor and videoconferencing capabilities. The university has committed to
finding additional headquarter space for BEACON’s second phase so that we may house more graduate
students and postdocs and have temporary space for collaborators from industry.
Center for Advancing Microbial Risk Assessment (CAMRA): MSU is the leader in a research project
funded by a $10 million grant from the U.S. Environmental Protection Agency and the Department of
Homeland Security to create the Center for Advancing Microbial Risk Assessment, a consortium of scientists
from seven universities with expertise in quantitative microbial risk assessment methods, biosecurity, and
infectious disease transmission through environmental exposure. CAMRA is a consortium of international
scientists, researchers and students who are interested in risk assessment for microbial agents and control of
infectious diseases. The vision of CAMRA is to be the global international collaborative for QMRA. The mission
of CAMRA is to provide a network that can link to critical data for running a QMRA, educational opportunities
for QMRA and QMRA case studies.
Diagnostic Center for Population and Animal Health (DCPAH): Relative to animal studies and translational
research, MSU's Diagnostic Center for Population and Animal Health (DCPAH) is one of the country's premier
and busiest veterinary diagnostic laboratories. From just over 9,700 cases when it first opened in 1973, the
facility now handles more than 200,000 cases and more than 1.2 million diagnostic tests per year. DCPAH is a
full-service veterinary diagnostic laboratory offering more than 800 tests in 11 service sections. In the more
than 30 years since its inception, DCPAH has become one of the country's premier veterinary diagnostic
laboratories, handling more than 220,000 cases involving approximately 1.5 million tests annually. The
Michigan State University Diagnostic Center for Population and Animal Health is an invaluable professional
resource, making quality, trusted, and comprehensive veterinary diagnostics widely available. Income from the
laboratory is reinvested in teaching, research, and outreach for the purpose of protecting human and animal
welfare domestically and around the world.
MSU Center for Ethics and Humanities in the Life Sciences (CEHLS): CEHLS has established bioethics
curricula for CHM, COM, CON and CHM students at MSU. CEHLS has 10 interdisciplinary faculty members
with degrees in philosophy, medicine, law, social sciences, and health services research. Faculty expertise of
includes the law and ethics of human subjects research, community perspectives in developing policy related
to emerging genetic knowledge; the ethical and social pitfalls in trying to use scientific evidence to shape
clinical judgment and practice; the effects of cultural differences in communicating complex new knowledge to
patients, in managing illness, and in designing health research; and interventions to improve patients’
understanding of and participation in decisions about complex medical choices. CEHLS administers the
Medical Ethics Resource Network of Michigan (MERN), a consortium of institutional ethics committees and
individuals active in research and clinical ethics around the state. MERN can provide a medium for developing
large-scale, multi-site studies that extend beyond the clinical campus communities.
MSU In Vivo Facility: This facility is a contract research organization serving academic and industry clients
while housed within Michigan State University. We enable important life sciences and biotechnology research
by providing high quality standard and specialized in vivo pharmacology models, investigative and drug
development services, medical device testing, and education. We are distinct from existing contract research
organizations in our ability to leverage the collective expertise of a major university. The MSU In Vivo Facility
offers efficient turnaround, competitive pricing, and the ability to connect directly with scientists involved in
studies. We routinely develop custom models and evaluations to fit a wide range of research needs. For
current Michigan State University faculty and staff, the MSU In Vivo Facility offers a specialized set of services
optimized for academic research.
Research Technology Support Facility (RTSF): RTSF Cores provide technical and analytical support for
Biomedical and Agricultural research at Michigan State University in Bioinformatics, Flow Cytometry,
Genomics, Imaging-IVIV, Mass Spectrometry, and Proteomics. The RTSF Cores and their services are
accessible to researchers at MSU and academic and research institutions throughout the world. Their mandate
is also to provide services to all Michigan Biotech and Pharmaceutical Companies, and they have institutional
customers from all over the globe. The RTSF consists of 6 cores, described below.
Bioinformatics Core: The RTSF Bioinformatics Core has high powered computers, as well as webdesigners, database experts, programmers, and systems administrators who understand biology and
biochemistry. Together they can analyze sequence and microarray data, develop a website to make the data
available to the general scientific community, and make sure that data on the web is safe from hackers and
backed up regularly. One of the hardest tasks in modern research is organizing large data sets from multiple
sources, such as might be generated from microarray and proteomic analysis. The RTSF Bioinformatics Core
is at the leading edge in designing and developing new data schemas for databases that allow researchers to
ask complicated questions and come up with insightful answers. Additional information can be found in the
Translational Science Base, Informatics Resources.
Flow Cytometry Core: The RTSF Flow Cytometry Core offers two flow cytometers to the MSU
community. Both are multiple laser based optical instruments that analyze cell populations for multiple
characteristics simultaneously. Flow cytometry is a laser-based technique that analyzes cell populations in
suspension. Flow cytometry analyses can simultaneously detect several biochemical parameters at rates up to
thousands of cells per second.
The Influx sorter can detect up to 14 colors with a maximum of 16 parameter. Forward scatter is collected from
a high sensitivity detector unit with resolution slightly below 0.2 um. The machine can sort up to 4 selected
populations. Sorted cells may be collected into a variety of tubes or plates.
The LSR II (Flow cytometer analyzer) can detect 9 colors with a maximum of 11 parameters and is useful for
analysis only. All parameters are correlated and analyzed simultaneously. Cells can be characterized
simultaneously through the detection of fluorescent probes for nuclear ploidy, cell cycle, apoptotic state,
expression of plasma membrane, cytoplasmic and nuclear proteins and other cellular characteristics The laser
excitation lines and common fluorochromes excited are: 1) 488 - FITC, PE, PerCp-Cy5, PE-Cy7. Other
flourochrome combinations are available at the PerCp-Cy5 detector. 2) GFP, YFP or RFP reporter proteins
can also be detected. 3) 405 - AmCyan, Pacifici Blue. 4) 640 - APC, Alexa 700, APC-Cy7.
Researchers save their data and analyze it using the Verity software line for post-acquisition data analysis.
Both flow cytometers are equipped with digital data acquisition electronics and DIVA data acquisition software.
Genomics Core: The RTSF Genomics Core (MSUGC) provides single gene to genomic scale DNA
sequencing services, DNA fingerprinting and genotyping, quantitative PCR, microarray printing and analysis.
The MSUGC has been providing genomic services for over a decade. Their mission is to keep pace with the
ever broadening world of genomic technology and make the research process as simple as possible. Services
include the following:
NGS Library size selection: The importance of increased read lengths for sequencers is directly proportional to
the proper NGS library insert size. Proper reads lengths are extremely important for applications like mate
pairs, chip-seq, PacBio preps, miRNA or proper genome sequencing libraries. Agarose gels and beads can
only provide so much precision in terms of size for sequencing libraries and are inferior to automated methods
for complete accuracy. The Genomics Core can now perform automated size selection accurately using the
Sage Science Blue Pippin. This platform uses gel cassettes to provide a full range of size selection options
between 90bp up to 50kb.
Cell ID: Short tandem repeat (STR) loci are among the most informative polymorphic markers in the human
genome. Additionally, STR profiles help to ensure the quality and integrity of human cell lines within the
scientific community as mandated by the NIH. The MSUGC provides cell identification services using the
ProMega Cell ID System which employs simultaneous co-amplification and three-color detection of ten loci in a
single tube. This kit is designed to run on the ABI 3730xl.
Mouse Genotyping: MSUGC utilizes the Mouse Genotyping kit technology from Kapa Biosystems. Rapid
extraction and amplification of DNA from tissue occurs in less than 1 hour followed by state of the art
electrophoresis instrumentation for rapid turnaround service.
Sample Shearing: Preparing high quality libraries for sequencing is paramount for obtaining good data and the
majority of protocols require fragmentation of the nucleic acid material to a specific size range. Mis-sizing of the
libraries can result in inaccurate quantification, poor cluster density and subsequently low quality data.
Shearing Services: The MSUGC provides shearing services for all NGS library types using the Covaris S2
Adaptive Focused Acoustic Disruptor. This platform enables improved preparation of small biological samples
up to 100ul in volume. Applications include DNA and chromatin shearing, tissue disruption and
homogenization, and cell lysis among others.
Sample QC: Library construction is the process of taking nucleic acid from its original state to a "library" that
can be run on a sequencing platform. Preparing high quality libraries is important for obtaining good data and
the MSUGC checks each sample before and after the library construction process to ensure it is of high
quality. Concentration, size and quality can be assessed using one of our microfluidics based platforms
Imaging IVIS Core: The RTSF Imaging IVIS Core Facility is the newest core to open to MSU
Researchers for quantitative bioluminescent and fluorescent (transmission and reflectance) imaging in
vivo and in vitro. The X-RAD 320 is a self-contained x-ray system for delivering radiation dosages safely and
effectively to specimens e.g. cell cultures, small animals. The IVIS Spectrum is a light tight imaging chamber
with integrated gas anesthesia and heated stage for quantitative bioluminescent and fluorescent imaging in
vivo and in vitro. Take advantage of bioluminescent and fluorescent reporters across the blue to near infrared
wavelength region using the IVIS Spectrums narrow band excitation and emission filters and spectral unmixing algorithms.
Mass Spectrometry Core: uses an array of mass spectral techniques for small molecule identification
as well as analyses and for Metabolomic profiling. The RTSF Mass Spectrometry and Metabolomics Core is an
‘open access’ resource where MSU researchers and Core staff perform chemical analyses for small molecules
and intact macromolecules. The Core features 12 autosampler-equipped mass spectrometers that collectively
provide GC-MS, LC-MS/MS, accurate mass (high resolution), and MALDI-TOF capabilities. Analyses
performed here typically involve compound identification, quantification, and statistical analysis. Core staff are
available to provide expert consultation regarding method development and data interpretation. Students and
other researchers are encouraged to become certified users of the instruments; training includes discussions
of theory and operation of the Core instrumentation; following training, users are provided 24/7 access to the
instruments. Methods currently running include nontarget metabolite profiling (metabolomics) and highthroughput profiling and quantification of amino acids, phytohormones, nucleotides signaling oxylipins,
structural lipids, and central and specialized metabolites. Capabilities for MALDI-TOF tissue and surface
imaging have also been developed. The Core performs analyses of samples from more than 100 institutions
from across North America.
Proteomics Core: The MSU Proteomics Facility provides resources to assist researchers in the
identification and characterization of proteins and peptides. Experiments from simple protein discovery to
complex differential proteome profiling and quantification as well as post-translational modification mapping
can be performed using our state-of-the art instrumentation and software.
The MSU Proteomics Facility utilizes the Bio-Rad Criterion size gels (8cm x 11cm; 11cm IEF) for 1D and 2DPAGE and various pH ranges and precast gel types are available. Gels can be stained with either Colloidal
Coomassie, Krypton fluorescent or mass spec compatible Silver stains. Additionally, the facility offers protein
and peptide separations in the liquid phase using the Agilent 3100 Offgel Fractionator or the Invitrogen ZOOM
IEF Fractionator. Using the Offgel Fractionator proteins/peptides can be separated into 12 or 24 distinct
fractions over various pH ranges. For larger protein loads, the ZOOM IEF fractionator can be used to generate
up to 7 pH fractions between pH 3 and 12. Any of these fractions can be further used for second dimension
SDS-PAGE separations or desalted and analyzed directly on a mass spectrometer.
The MSU Proteomics Facility contains two state of the art mass spectrometers. The workhorse of the facility is
a ThermoScientific LTQ Linear Ion Trap mated to a Waters nanoAcquity UPLC and Bruker/Michrom
CaptiveSpray nanospray ionization source. This machine combines fast, sensitive ion detection and MSn
capabilities with exceptional LC gradient stability and resolution for rapid protein and peptide identifications on
both large and small scale. For more specific experiments we also operate a ThermoScientific Q-Exactive
mass spectrometer with an attached EASY-nLC UPLC and flex-spray nano-spray ionization source. This
system provides optimized split-free peptide separation, high-performance quadrupole ion selection and highresolution, accurate-mass (HR/AM) Orbitrap detection for unprecedented peptide detection, characterization
and quantification. Spectral processing, matching and quantification are done using both the Mascot Distiller
software suite with the Mascot search algorithm and the MaxQuant/Andromeda software suite. Results are
further validated and visualized using the Scaffold software package.
Medicinal Plant Genomics Resource: Natural products from plants serve as rich resources for drug
development with almost 100 plant-derived compounds in clinical trials in 2007. Plant derived natural products
have had a profound and lasting impact on human health and include compounds successfully used for
decades such as digitalis, Taxol, vincristine, and morphine isolated from foxglove, periwinkle, yew, and opium
poppy, respectively. The enormous structural diversity and biological activities of plant-derived compounds
suggest that additional, medicinally relevant compounds remain to be discovered in plants.
While plant natural products continue to be a prime target for drug development, as evidenced by the number
of ongoing clinical trials, the clinical potential of these compounds is often curtailed due to low production levels
in plant species. For example, use of the blockbuster drug Taxol almost stopped in the early 1990's because
the primary source, yew tree bark, could not be used as a sustainable source of the drug. In this particular
instance, a Taxol precursor happened to be more readily available in a renewable part of the tree, and a semisynthetic protocol could be developed to convert it into the drug. While fortuitous, more generalized solutions,
such as metabolic engineering of effective plant and microbial production platforms, are urgently needed to
ensure that the wealth of bioactive compounds found in plants enter the clinical pipeline and find widespread
use in medicine.
High throughput transcriptome sequencing approaches provide a straightforward means for accessing the
gene content in organisms with large genomes (i.e. > 100 Mb). Essentially any tissue (independent of genome
size and availability of genetic or molecular tools in the organism) can be used to generate cDNAs from mRNA
populations and sequenced to generate Expressed Sequence Tags (ESTs) that are assembled into a nonredundant set of sequences (contigs and singleton ESTs) to represent the transcriptome. The transcriptome
sequences are then annotated for putative function using a suite of bioinformatic approaches such as
sequence searches of protein databases, motif/domain identification, biochemical pathway mapping, and
subcellular localization predictions. Transcript abundance data can also be used to provide in-depth expression
profiles of individual genes on a per tissue/treatment basis. The deduced function, coupled with expression
frequency, can facilitate identification of candidate genes pertinent to the pathway of interest as well as non-
pathway targets (e.g. primary/intermediary metabolism) whose expression is consistent with synthesis of
compounds.
Trichrome- The Solanum Trichrome Project: Secretory and glandular trichomes (SGTs) populate the aerial
surfaces of approximately 30% of all vascular plant species. These uni- and multi-cellular appendages are
proposed to play a critical role in plant protection against various biotic and abiotic stresses including herbivore
attack, pathogen infection, extreme temperature, and excessive light. One of the most remarkable features of
SGTs is their capacity to synthesize, store, and secrete large amounts of secondary metabolites. Because they
are not essential for plant viability, SGTs provide a unique opportunity to study complex and specialized
metabolic pathways that operate within the confines of a simple and highly accessible developmental structure.
It is noteworthy that many trichome-borne compounds have significant commercial value as pharmaceuticals,
fragrances, food additives, and natural pesticides. For this reason, the prospect of exploiting SGTs as
“chemical factories” to produce high-value plant products has recently captured the attention of plant
biochemists and biotechnologists alike. Realization of this goal will be facilitated by genome-scale research
focused on the identification of genes that control the development and biochemical functions of SGTs.
Table 1
Hospitals
McLaren Bay Region (Bay City)
Community Health Center of Branch
County
Beaumont Health System
Botsford Hospital
Detroit Medical Center, Osteopathic
Division
Detroit Metro Urological Surgical
Consortium
DMC Huron Valley- Sinai Hospital
Garden City Hospital
Henry Ford Macomb Hospitals
Henry Ford Wyandotte Hospital
McLaren Macomb
McLaren Oakland
Mercy Memorial Hospital System
Oakwood Healthcare System
St. John Providence Health SystemOsteopathic Division
St. Joseph Mercy Oakland
St. Mary Mercy Hospital
Genesys Regional Medical Center
Hamilton Community Health Network
Hurley Medical Center
McLaren- Flint
Metro Health Hospital
Pine Rest Christian Mental Health
Services
Mercy Health Saint Mary's
Spectrum
Region
CHM
COM
Bay City
Coldwater
X
X
Detroit
Detroit
Detroit
X
X
X
Detroit
X
Detroit
Detroit
Detroit
Detroit
Detroit
Detroit
Detroit
Detroit
Detroit
X
X
X
X
X
X
X
X
X
Detroit
Detroit
Flint
Flint
Flint
Flint
Grand
Rapids
Grand
Rapids
Grand
Rapids
Grand
X
X
X
X
X
X
X
X
X
X
X
X
Hillsdale Community Health Center
Allegiance Health
McLaren- Lansing
Sparrow Healthsystem
Covenant Healthcare (Saginaw)
Gratiot Medical Center (Alma)
Mid Michigan Medical Center- Clare
Mid Michigan Medical Center- Gladwin
Mid Michigan Medical Center- Midland
St. Mary's (Saginaw)
Mercy Health Hackley CampusMuskegon
Mercy Health Muskegon
Lakeland Healthcare
ProMedica Hospital (Toledo)
Alpena Regional Medical Center
Charlevoix Area Hospital
Kalkaska Memorial Health Center
McLaren Northern Michigan (Petoskey)
Mercy Hospital Cadillac
Mercy Hospital Grayling
Munson Medical Center
Otsego Memorial Hospital (Gaylord)
Paul Oliver Memorial Hospital
(Frankfort)
West Shore Medical Center (Manistee)
Marquette General Hospital
Rapids
Hillsdale
Jackson
Lansing
Lansing
Midland
Midland
Midland
Midland
Midland
Midland
Muskegon
Muskegon
St. Joseph
Toledo
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Traverse City
Upper
Peninsula
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Download