University of Pittsburgh
School of Pharmacy
Department of Pharmaceutical Sciences
335 Sutherland Drive, 206 Salk Pavilion, Pittsburgh, PA 15261
Lab website: www.CBLigand.org/xielab
Computational Chemogenomics Screen Center
Tel: 412-383-5276 Fax: 412-383-7436
Email: xix15@pitt.edu xxie678@hotmail.com
www.CBLigand.org/CCGS www.CBLigand.org/CDAR
August 18, 2015
Attn: Jenny Wakida, DKICP Dean Search
200 W. Kawili Street, Hilo, HI 96720
uhhdkicp@hawaii.edu Dr. Sue Jarvi, jarvi@hawaii.edu
RE: Dean (UH Hilo/College of Pharmacy) Position #89428
Dear Search Committee:
Please consider, in strictest confidence, this letter as an application for the Dean Position at the
College of Pharmacy, University of Hawaii at Hilo, described in your recent advertisement.
I am an Associate Dean for Research Innovation at School of Pharmacy, a tenured Professor of
Pharmaceutical Sciences/Drug Discovery Institute, and a PI of an integrated Medicinal Chemistry
Biology laboratory of CompuGroup, BioGroup and ChemGroup (www.CBLigand.org/XieLab) at
University of Pittsburgh. I am a member of the US FDA Science Board (the highest advisory
committee in the FDA). I am a Founding Director of Computational Chemical Genomics Screening
Center (www.CBLigand.org/CCGS), and a Director/PI of NIH National Center of Excellence for
CDAR (www.CDARCenter.org). I hold joint positions at Dept of Computational Biology and Dept
of Structural Biology, and Pitt Cancer Institute MT/DD Program. I am also an Editorial Advisory
Board member for AAPS Journal and American Journal of Molecular Biology, and Associate Editor
of BMC Pharmacology Toxicology. I am a recipient of 2014 AAPS Award for Outstanding
Research Achievements.
Thus, I believe that my Executive MBA leadership training, PhD in Pharmaceutical Sciences,
MD Pharmacy and my 20 years known-how teaching/research/administrative experience in
leading/managing multiple projects and center resources during my tenures, as Professor and
Director of three Research Centers in three top colleges of pharmacy (University of Connecticut,
University of Houston and University of Pittsburgh) as well as my experience as an Associate Dean
of the School of Pharmacy University of Pittsburgh, plus my external out-reach experience with
pharma/biotech for fund raise and consortia with the FDA and NIH Labs will make me a
qualified candidate for the position. I would like to highlight my career achievements below:
(Leadership and Ability to Communicate Effectively with Internal and External Constituencies)
As an Associate Dean for Research Innovation, I have successfully led as a PI/Director and
secured $5.4 million NIH center grant, and established NIH National Center of Excellence for
Computational Drug Abuse Research (CDAR) (www.CDARcenter.org). This is a joint “BigData” computational initiative between the University of Pittsburgh and Carnegie Mellon University.
I have taken in charge of establishing consortia with FDA and close collaborations with NIH
intramural research laboratories, including “Pitt/FDA Chemogenomics Knowledgebase for Allergen
Research”. I have actively reached out to Pharma/Biotech companies, including recent meetings
with Pfizer, Eli lily and Oxis etc. With my past and present connections and working experience
with Pharma/biotech companies, I am able to engage a new initiative of $2.5 million to fund our
multiple myeloma and osteoporosis drug discovery research under the signed Sponsored Research
Agreement recently.
Page 2/6
I have a history of leadership for collaborative research center grants. I was co-PI/Core Director
of the NIH-funded P50 center grant, Pittsburgh Center for Chemical Methodologies & Library
Development (PCMLD, Director: Peter Wipf) and NCI/SAIC funded University of Pittsburgh Center
for Diversity Chemistry (UP-CDC, Donna Huryn, Director). I was co-PI of the Pittsburgh Molecular
Library Screening Center (PMLSC, Director: John Lazo) funded by NIH Roadmap Initiative. I was
PI and Director leading X02 Pittsburgh Cheminformatics Center grant by organizing a team of 21
scientists from Pitt, CMU, Pittsburgh Super Computer Center and Duquesne University. I hold
several joint faculty positions, including at the Departments of Computational Biology, Department
of Structural Biology, and Pittsburgh Cancer Center; and the joint CMU-Pitt Ph.D. Computational
Biology Training Program, Molecular Biophysics & Structural Biology Training Program and
Cancer Center MT/DD training Program at Pitt.
Prior to Pitt, I was a tenured faculty at College of Pharmacy, University of Houston (UH). I also
led a P20 Houston Pharmacoinformatics Research Center grant with a team of 20 experts and
scientists from University of Houston, Rice University, University of Texas Health Science Center,
MD Anderson, and Baylor College of Medicine. I served as an Advisory Committee Member and
training faculty member for the NIH funded Pharmacoinformatics Training Program at Houston Gulf
Coast Consortium (GCC) (Dr. George Stancel, Dean of Graduate School). In addition, I held several
joint faculty positions, including at the Institute for Molecular Design, Texas Learning Computing
Center (TLCC), the Keck Center for Computational & Structural Biology, and a Director of the
Chemistry Coordinating Unit for GCC-Chemical Genomics Screening Center (Dr. P. Davis, VP).
Prior to UH, I was a Director of IMS NMR Laboratory of University of Connecticut (UCONN) that
was well funded by NIH and pharma/chemical companies. All of above demonstrated that I was able
to lead and direct multiple NIH research projects and manage the center resources successfully by
bringing both federal funding and pharma contracts as well as providing my expertise and
collaborations with scientists within the institute and the outside.
Furthermore, I have received formal EMBA education, and I have acquired extensive leadership
and management skills/experience in leading/participating joint research center grants as described
above. Such leadership and management capabilities have been built up through my working
experience as Director/Funding Director of three research centers in three institutes, including IMS
NMR Center at University of Connecticut, Founding Director of Pharmacoinformatics Research
Center (PIRC) at the UH College of Pharmacy, and current Pitt Computational System
Chemogenomics Screening Center. These centers have served as a pivot point of synergetic
collaborations for teaching/training and research. As an Associate Dean, I am also a member of
Leadership and Steering Committee and a member of Planning and Budgeting Committee at Pitt
School of Pharmacy. These committee members are appointed by Dean/institute as our institutional
think-tank for school planning and development.
All of above have demonstrated my formal MBA training and strong dynamic leadership
and ability to plan, organize and communicate effectively with internal and external
constituencies, with over 15 years of progressively responsibility administrative experience as
Center Directors and Associate Dean of School of Pharmacy.
(Xie letter
page 3/6)
(Distinguished Scholarship, Research Publication, Professional Activity and Achievements)
My scientific research achievements and scholarship have been widely recognized nationally
and internationally. I am a recipient of 2014 AAPS Award for Outstanding Research Achievements.
I am a member of the US FDA Science Board Advisory Committee (the highest advisory committee
in the FDA). I am an Editorial Advisory Board member for AAPS Journal and American Journal of
Molecular Biology, and Associate Editor of BMC Pharmacology Toxicology. I am a Charter
Member of NIH BPNS Study Section. I was ad hoc expert reviewer for UK MRC foundation, the
Wellcome Trust Fund, the Netherland Organization for Scientific Research Council, the Austrian
Science Fund (FWF) Erwin Schrödinger Fellowship, and the Chinese Natural Science Foundation. I
hold/held honorary professorship in top institutes and colleges of pharmacy in China, including
Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Stem Cell
Medical Center; and Shanghai Jiaotong University. I was an invited International Assessment
Panelist for Fudan University College of Pharmacy, a member of the Board of Directors of the
Chinese Association of Professionals in Science and Technology, and a Chair of the CAPSTBiomedical & Pharmaceutical Society.
I have had a significant track of successful extramural funding (both Federal and industrial) and
research productivity records. As a PI of an integrated Medicinal Chemistry Biology laboratory of
CompuGroup, BioGroup and ChemGroup (www.CBLigand.org/XieLab), and PI/Director of NIH
Center of Excellence for computational drug abuse and neurodisorder research, my research team is
known for our pioneering research for the development of internationally recognized diseases
domain-specific chemogenomics knowledgebases, which is an integrated platform of “Big Data to
Knowledge” computational chemogenomics-based target identification and system pharmacology for
translational research. Over the years, I have acquired extensive expertise in computational
chemistry, structure biophysics, molecular biochemistry and medicinal chemistry synthesis as well as
chemogenomics virtual screening, in silico design and in vitro bioassay for small molecule drug
discovery and receptor binding/signaling mechanism studies with over 100 publications of peerreviewed research articles, book chapters, reviews and patents of new drug invention. Our recent
work on Alzheimer’s disease specific chemogenomics database was on 2014 coverpage story of a top
peer-reviewed ACS journal. The innovation work includes GPU-accelerated cloud computing
TargetHunter program for drug target identification (www.CBLigand.org/TargetHunter) (2013 AAPS
special theme issue). My lab was the first to discover/patent INK4C-targeting small molecule
inhibitors for hematopoietic stem cell expansion (Nature Comm 2015), was the first discover/patent
p62ZZ chemical inhibitors for multiple myeloma (Nature Leukemia 2015). We also reported/patented
novel ligands specific to cannabinoid CB2 receptor for osteoporosis and cancers. Our invention
discovery patents have been successfully licensed out to Biotech/Pharma.
Overall, our developed integrated cloud computing knowledgebases help to bridge the
knowledge gap between biology and chemistry, and to facilitate target identification, drug
repurposing and system pharmacology analyses on a chemogenomics scale for precision medicine
drug discovery. As a result, I was a recipient of 2014 AAPS Award for Outstanding Research
Achievements.
In addition, my laboratory has developed/published GPU-accelerated cloud computing and
machine-learning algorithms and drug TargetHunter programs (www.CBLigand.org/TargetHunter)
as well as chemogenomics knowledgebases for diseases-specific, including Alzheimer’s, Parkinson,
(Xie letter
page 4/6)
Drug Abuse, Multiple Myeloma, Hepatic Fibrosis, as well as immune modulators, anti-tussive, and
anti-thrombosis etc) (www.cbligand.org/CCGS/research.php), which have been used by broad
scientific communities, particularly for pharmacogenomics and natural product research
laboratories/centers nationally and internationally. We have recently signed a consortium agreement
with FDA to develop allergy database and allergen predictor. In addition, I believe that our
developed/published cloud computing and cloud sourcing chemogenomics databases and
algorithms/programs could be easily integrated with the existing center at UH College of Pharmacy
and cross campus.
My strong track of records of scholarly activities, publications in pharmaceutical, natural
product and biomedical sciences research using our established integrated medicinal
chemistry, computational, biophysical, biochemical and chemical approaches has proved my
experienced management in directing and communicating with research
laboratories/centers/institutions for productive research.
(Training, Education and Consultations)
I have had a significant record of teaching and training experience in mentoring undergraduate,
PharmD and graduate students/Postdocs (see the number of trainees my CV). I am currently a
member Graduate Program Council in Pitt School of Pharmacy. I was Chair of Graduate Admission
Committee and Chair of the Distinguished Lecture Series Committee for Pitt School of Pharmacy.
Prior to Pitt, I served as a member or chair in many institutional committees, including the Pharm D
Curriculum Committee, the Clinical Track Faculty Policy and Faculty Recruiting Committee. I also
served as an Advisory Executive Committee Member and co-PI for the NIH-funded
Pharmacoinformatics Training Program at Houston Gulf Coast Consortium (GCC). I have also
known in-depth and experienced in-person the pharmacy education/training and research in three
colleges of pharmacy systems, either as a pharmacy undergraduate, graduate student, and faculty
member during my tenure. I received my Pharmacy MD degree in 1982 from the College of
Pharmacy, Second Military Medical University in Shanghai, China, and my Ph.D. in Pharmaceutical
Sciences from the School of Pharmacy, University of Connecticut in 1993. I received an Executive
MBA degree in 2003. As a faculty, I was the recipient for service award for Exemplary Service in
NSF Computational Biology Undergraduate Research Program in 2011. I have taught or served as
course master/coordinator for many PharmD and graduate courses, and have mentored and trained
many postdocs, graduates and undergraduate students. Currently, I have two undergraduates, three
MS graduate, three PhD graduate student and four Postdoc Research Associates in my laboratory
while I am staying active in teaching three courses for this semester. I should also mentioned that I
have gone through three times for ACPE Accreditation Self-Study and ACPE Accreditation Site
Visits during my tenure at three top schools of pharmacy in the US.
(National and International Service and Network Connections)
I am currently charter member of NIH BPNS Study Section Panel, and was ad hoc reviewers
for national and international grants/foundations, including NIH, UK MRC Foundation,
Netherlands Organization for Scientific Research (NWO) Council for Chemical Sciences (CW),
The Wellcome Trust Fund, Sir Henry Wellcome Fellowship London, UK, the Austrian Science
Fund (FWF) Erwin Schrödinger Fellowship, and the Chinese Natural Science Foundation. I was
an invited guest editor for AAPS Journal theme issue 2013. I am an Editorial Advisory Board
(Xie letter
page 5/6)
Member for AAPS Journal and American Journal of Molecular Biology, and Associate Editor of
BMC Pharmacology Toxicology. I was invited by many scientific journals ass ad hoc reviewers
as well as consultants for pharma and biotech companies.
I am an invited expert panel reviewer for Chinese Natural Science Foundation meeting. I was
invited by Fudan University to serve as one of the five International Assessment Panelists for
evaluation of their college of pharmacy teaching and research programs. Most recently, I have
played a key role in organizing trips for our school administrators to Shanghai, Beijing and
Guangzhou China and setting up exchange PharmD and clinical pharmacy programs for our
school with top universities and hospital pharmacies in China. In fact, my suggestion to develop
MS degree program has expanded our graduate program, which has generated significant tuition
revenues and enhanced our PhD graduate program in return.
As a new Dean for UH Hilo College of Pharmacy, I will face many existing and new
challenges, particularly the fact that widely publicized congressional cutbacks to the NIH have
generated significant negative impact to many laboratories and institutes. Thus, I will work
closely with UH Hilo Administrative office, Departmental Chairs as well as faculty members to
develop strategic plans to maintain/enhance the current research and educations at UHH COP in
order to promote new research and make a full use of the available resources at campus.
In addition to the qualifications above, I would like to propose three immediate initiatives as
a new starter at UHH, briefed as below.
An immediate plan is to “Reach out and diversify” for research programs. Considering the
federal budget cuts, we need to reach out for industrial and even international funding, and build
synergic collaboration to submit joint center grants and program projects through team
collaborations. I have/had, in addition to my own NIH funding, contracts/consortia support in
the past from pharma companies, and close collaboration projects with institutes in China and
other countries. Currently, I have two Chinese Fellowship-supported Postdocs in my laboratory.
I am currently XieHe Honorary Endowed Chair Professor of Chinese Academy of Medical
Sciences & Peking Union Medical College. I also have/had held adjunct Professor Title in
colleges of pharmacy at top Universities in China, including Fudan University, Shanghai
Jiaotong University, Zhejiang University, and Sun Yat-Sen University. These international
network connections have also helped our PhD program and student recruitment at Pitt.
Another initiative is to “Build MS to support PhD”. NIH budget cuts caused many PIs loss
funding to support their PhD graduate students. High quality graduate students are very important
and critical to continue the research projects for publication and new NIH funding applications.
During my time as Admission Chair and currently as a member of Graduate Program Council, I
foresee the potential negative impact to our PhD program, and thus I proposed to the department
chair and Dean to build and expand non-thesis MS program, from zero to almost 35 MS graduate
students now. These MS students from China, India and Saudi etc have generated plausible
tuition revenues to our university, and in return, that helps our PhD program financially,
particularly to the PI who lost their NIH funding due to NIH budget cuts or need bridge fund to
retain their junior/senior PhD graduate students. Such “Build MS to support PhD” strategy also
helps to expand our PhD programs. In particular, MS pools have prepared high quality PhD
candidates for our further recruitment.
(Xie letter
page 6/6)
Another possible initiative is to build a clinical pharmacist/director training
programs/workshops with countries, such as China where it has huge demands. I have
organized two trips for Pitt SOP to visit the top-tier hospitals and universities in Shanghai and
met 12 Directors/Associate Directors of the hospital Departments of Pharmacy (many of them are
my classmates or college-mates in China). I also should mentioned that I have two Saudi
Fellowship-supported graduate student researchers in my laboratory as I have served as external
advisor and promotion reviewers for Saudi Institutes and also retained close interactions with a
former UH Alumni Dr Alesia who is currently Academic Advisor of Royal Embassy of Saudi
Araba at Washington DC. Pitt SOP has actively engaged with Saudi institutes for exchange
programs.
All of these above have demonstrated my collaborative and dynamic leadership ability and
interpersonal communication skills for directing and leading research and education.
Overall, my system educations in Pharmacy MD/PhD and MBA leadership/management, year’s
working/administrative experience, and extensive graduate/PharmD teaching and research, have
taught me how to plan and lead an organization while sharpening my ability to analyze research,
teaching/education, and technological innovation in the context of strategic planning, organizational
design, and national/global competition. Thus, with my solid experience, qualifications, and
dynamic teamwork personality as well as my self-motivated and hardworking nature, plus my
teaching and research strengths and director-working experience from three top pharmacy schools
(UCONN, UH and UPitt) in the nation and currently as Associate Dean, I have a confidence to lead
and work with the faculty and staff teams in the College of Pharmacy, to reinforce the first-class
professional PharmD programs, and to develop/strengthen the multidisciplinary pharmaceutical and
clinical sciences research programs in the UHH College of Pharmacy.
I am attaching my expanded C.V., and indicated some references below. I have deliberately not
included my current boss because I respectfully ask that this application be kept confidential until we
know whether the committee shares my feeling that this is an excellent match. Should there be
serious interest, you may contact me, and I will request that the letters be sent directly to you.
Thank you again for your time and consideration and look forward to your response.
Sincerely yours,
Xiang-Qun (Sean) Xie, MD, PhD, EMBA
Associate Dean for Research Innovation, School of Pharmacy
Professor of Pharmaceutical Sciences/Drug Discovery Institute
Director of Computational Chemical Genomics Screening (CCGS) Center
Director of NIH National Center of Excellence for Computational Drug Abuse Research
Email: xix15@pitt.edu Cell:
Lab/Center: www.CBLigand.org/Xielab www.CBLigand.org/CCGS www.CBLigand.org/CDAR
OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME:
Xiang-Qun (Sean) Xie, MD, Ph.D., EMBA
eRA COMMONS USER NAME (credential, e.g., agency login):
POSITION TITLE: Professor and Associate Dean for Research, Director of NIH CDAR Center
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
Completion
DEGREE
FIELD OF STUDY
INSTITUTION AND LOCATION
Date
(if applicable)
MM/YYYY
MIT Magnet Lab., MIT, MA/Univ. of Conn., CT
Post-doc.
1993-1995
Biophysics/NMR
SBA, University of Connecticut, Storrs, CT
E.M.B.A.
2001-2003
Executive MBA
Ph. D., M.S.
1987-1993
Medicinal Chemistry
MD
1978-1982
Pharmacy
Pharmacy, University of Connecticut, Storrs, CT
Second Military Medical University, Shanghai, China
A. Personal Statement
As an Associate Dean for Research and a PI/Professor of an integrated research laboratory of CompuGroup,
BioGroup and ChemGroup (www.CBLigand.org/xielab), my research interests are keen on computational and
experimental chemogenomics knowledgebased drug discovery and cannabinoid neuro- and immune-signaling
mechanism studies. My expertise lies in developing know-how technologies/publications of computational
chemistry/biology, medicinal chemistry design/synthesis, and biophysics/biochemistry. I have also expand my
expertise and developed GPU-accelerated cloud computing and machine-learning TargetHunter© programs, as
well as chemogenomics knowledgebases that are domain-specific (including cannabinoid, drug abuse and
stem cell molecular information) and disease-specific (including Alzheimer’s, Trauma Brain Injury (TBI),
Osteoporosis, Multiple Myeloma etc (www.cbligand.org/CCGS/research.php). The goal is to address fundamental
challenges in predicting the bioactivity and pharmacological properties of chemicals/drugs on a genomics scale
and validate them by experimental bioassays for signaling pathway, system pharmacology studies and drug
discovery. As a Professor of Pharmaceutical Sciences/Drug Discovery Institute and Computational Biology at
UPitt, and joint faculty of Carnegie Mellon University/University of Pittsburgh (CMU/Pitt) Computational Biology
PhD Program, I have successfully developed integrated approaches of GPCR structural biophysics,
computational chemical genomics/bioassay validation and medicinal chemistry, as well as small molecule
chemical probe discovery and development for neuro-disorders, osteoporosis, multiple myeloma diseases, and
hematopoietic stem cells expansion. Among our discoveries, three patents of our new chemical agents/drugs
have been successfully licensed to Biotech/Pharma companies. As Founding Director of Computational
Chemical Genomics Screening Center at UPitt, I served as co-PI and core Director on two NIH-funded center
grants (PCMLD NIH P50 and UP-CDC NCI/SAIC) and served as co-PI on NIH PMLSC grant. Most recently, I
have begun to serve as Director/PI of the NIDA National Center of Excellence for computational drug abuse
and neurodisorder disease research. I am also a charter member of the FDA Science Board Advisory
Committee. All of these have awarded him a 2014 AAPS Outstanding Research Achievement Award. All of
these have prepared me to fulfill my role as PI in this project in all aspects of the research.
B. Positions and Honors
Positions and Employment
2014-pres. Associate Dean for Research Innovation, School of Pharmacy, University of Pittsburgh, PA
2014-pres. Director/PI of NIH National Center of Excellence for Computational Drug Abuse Research, PA
2006-pres. Professor, Dept of Pharmaceutical Sciences, Drug Discovery Institute, University of Pittsburgh, PA
2011-pres. Director, Computational Chemical Genomics Screening Center, University of Pittsburgh, PA
2006-pres. Faculty, Dept of Structural Biology, School of Medicine, University of Pittsburgh, PA
2007-pres. Faculty, Joint Carnegie Mellon University/Univ. of Pittsburgh Computational System Biology Ph.D.
Program, School of Medicine, University of Pittsburgh, and Pittsburgh Supercomputing Center, PA
2011-pres. Co-PI and Director of Cheminformatics Core of NIH NCI/SAIC Chemical Biology Consortium –
UPitt Chemical Diversity Center (UPCDC), University of Pittsburgh, PA
2008-pres. Co-PI and core co-director of NIH Pittsburgh Center for Chemical Methodologies & Library
Development (PCMLD), Dept of Chemistry, University of Pittsburgh, PA
2006-2008 Faculty and co-PI, NIH Pittsburgh Molecular Library Screening Center (UPMLSC), School of
Medicine, University of Pittsburgh, PA
2008-pres. Faculty member, Pittsburgh Cancer Institute, the Molecular Therapeutics and Drug Discovery and
Development program, School of Medicine, University of Pittsburgh, PA
2003-2006 Associate Professor, College of Pharmacy, University of Houston Texas
2005-2006 Founding Director, Pharmacoinformatics Research Center (PIRC), College of Pharmacy, UH, TX
2005-2006 Director, Chemistry Coordinating Center (Chemistry Unit) of the Chemical Genomics Screening
Center at Houston Texas, Gulf Coast Consortium (GCC), Houston, TX
2004-2006 Faculty, GCC Magnetic Resonance Program; Keck Center for Computational & Structural Biology;
Institute for Molecular Design and Texas Learning & Computation Center(TLCC), Houston, TX
2005-2006 Executive Committee Member, NIH Pharmacoinformatics Training Program Houston TX
2000-2003 Director, IMS NMR Laboratory/Associate Research Professor, University of Connecticut, CT
1995-2003 Adjunct Assistant/Associate Professor, School of Pharmacy, University of Connecticut, Storrs, CT
Other Experience and Professional Memberships
2015-2018 Member of the FDA Science Board Advisory Committee, the United States Food and Drug
Administration (FDA)
2015/3/19 Member of NIH Program Project Site Visit Renewal Panel ZRG1 BCMB-S (40)
2013-2015 Invited Expert Panel Reviewer of Key Program of Chinese Natural Science Foundation
2011-2015 Charter Member of NIH Biophysics of Neural System (BPNS) Study Section Review Panel
2012-pre Editorial Advisory Board member for AAPS Journal, a Guest Editor of AAPS Journal, Theme Issue
“New Paradigms in Pharmaceutical Sciences: In Silico Drug Discovery”.
2011-pre Editorial Board Member, American Journal of Molecular Biology
2012-pre Associate Editor of BMC Pharmacology and Toxicology journal
2010Invited Ad Hoc reviewers for the Molecular and Cellular Medicine Board (MCMB), MRC
Foundation, United Kingdom; Netherlands Organization for Scientific Research (NWO), Council for
Chemical Sciences (CW); The Wellcome Trust Fund, Sir Henry Wellcome Fellowship, London, UK
2010
Invited Special Emphasis Panelist, NIH National Institute on Drug Abuse (NIDA) (ZDA1 MXL-F)
2010
Session chair/invited speaker, International Medicinal Chemistry Symposium, Beijing, China
2009
Invited International Assessment Panelist, Fudan University College of Pharmacy, China
2008Chair, the Distinguished Lecture Series Committee, School of Pharmacy, University of Pittsburgh.
2008Chair, Graduate Admission Committee, School of Pharmacy, University of Pittsburgh
2007Ad hoc member, NIH BLIRC Study Section, National Library of Medicine
2005-2009 Member, NIH Biophysical and Biochemical Science Study Section (ZRG1)
2006Invited Expert Panel Reviewer, Chinese Natural Science Foundation
2006
Chair and organizer, ACS SWRM – NMR Symposium “Challenges of NMR Structural Proteomics”
2005-2006 Member, the Board of Directors of the Chinese Association of Professionals in Science and
Technology (CAPST) and a Chair of the CAPST-Biotechnological and Pharmaceutical Society
2004
International Structural Genomics & Rational Drug Design on Membrane Proteins Consortia
2004
Informatics Advisory Committee of GCC Houston Small Molecules Library Screening Center
2001-2003 Ad hoc panel reviewers for the intramural grant UConn, and NIH Cutting Edge Basic Research
2000-2003 Consultant (Boston Scientific Corp., Pfizer, Roger Chemicals, etc)
Honors and Awards
• 2014 AAPS Outstanding Research Achievement Award. • Exemplary Service Award in NSF Fellowship
Computational Biology Undergraduate Research Program. • XieHe Scholar Honorary Professor, Chinese
Academy of Medical Sciences & Peking Union Medical College. • Nominee for 2006 Research Excellence
Award. • Top 20 article award in 2004. • 1998-2003 NIH FIRST Award (NIH Young Investigator Award). •
1999 Chinese Government Natural Science Foundation (CNSF) Award – CNSF. • 1999 North America
China Bridges International Award – CBI. • 1998 Chinese Government Educational Bureau Foundation
Award – CEBF. • 1994, 1995 NSF Research and Education fund Program for Faculty Enhancement- NSF. •
1994, 1996 Minority Staff Development Fund Program Award - University of Connecticut. • 1992 PHI
KAPPA PHI Honor Society - UConn. • 1991 Summa Award for academic excellence - UConn. • 1991
Special Award for NMR service - UConn. • 1984 Outstanding Teacher Honor - The 2nd Medical University,
Shanghai, PRC.
C. Contribution to Science
1. Alzheimer’s Disease-specific chemogenomics knowledgebase for signaling pathway studies
Xie’s lab is known for its pioneering research for the development of diseases domain-specific
chemogenomics knowledgebase database, an integrated platform of target identification, system
pharmacology and translational research. These include Alzheimer’s, Drug Abuse, Cardiovascular,
Osteoporosis, Multiple Myeloma, Stem Cells, Diabetes databases, etc. (www.cbligand.org/CCGS/research.php).
His recent work on Alzheimer’s disease specific chemogenomics knowledgebase represents an innovative
“data to knowledge” system accessible at www.CBLigand.org/AD/, and has won 2014 coverpage story of a top
ACS peer-reviewed journal1. His lab is in process to develop HD (Huntington), PD (Parkinson) and TBI
(Trauma Brain Injury) specific chemogenomiocs database (b-version available), implemented with his
developed computational algorithms/tools, including the GPU-accelerated2 TargetHunter© program for drug
target identification (2013 AAPS special theme issue, www.CBLigand.org/TargetHunter)3, machine learning
Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps (LiCABES) algorithms for GPCR ligand
selectivity or functionality prediction (JCIM 2012, 2013)4, 3D chemistry-space matrix-based compound library
acquisition and prioritization (CLAP) profiling algorithm for constructing/purchasing structurally diverse
chemical libraries (2013 ACS Comb. Science coverpage), and molecular fingerprint-based artificial neural
network algorithm for QSAR analysis, HTDocking, and BBB-predictor (www.cbligand.org/xielab/technology.php).
1. Liu, HB, Wang, L, Su, WW and Xie* X.-Q., ALzPlatform: An Alzheimer’s Disease Domain-Specific
Chemogenomics Knowledgebase for Polypharmacology and Target Identification Research. J Comput
Info Modeling. 2014, 54(4):1050-60. (Coverpage of the issue).
2. Ma, C, Wang, LR, Xie, XQ* “GPU Accelerated Chemical Similarity Calculation for Compound Library
Comparison” JCIM, 51 (2011), 1521–1527
3. Wang L, Ma C, Wipf P, Liu H, Su W and Xie X-Q*. “TargetHunter: An In Silico Target Identification Tool
for Predicting Therapeutic Potential of Small Organic Molecules Based on Chemogenomic Database”.
AAPS J. 2013, 15, 395-406 (AAPS Special theme issue)
4. Ma C, Wang LR, Yang P, Tong Q, Myint KZ, and Xie X-Q*. “LiCABEDS II. Modeling of Ligand
Selectivity for G-protein Coupled Cannabinoid Receptors”. J. Chem. Inf. Model., 2013,
53(1):11-26
5. Xie X-Q*, Wang L, Liu H, Ouyang Q, Fang C and Su W. “Chemogenomics Knowledgebased
Polypharmacology Analyses of Drug Abuse Related G-Protein Coupled Receptors and Their Ligands”.
Front. Pharmacol.(Neuropharmacology), 2014, 5:3.
2. FIRST INK4C CHEMICAL MODULATORS FOR HEMATOPOIETIC STEM CELL (HSC) EXPANSION
Xie’s Lab was the first to discover and report (Nature Comm 2015)1 a small molecule that inhibits p18INK4C
(or p18), a stem cell regulator protein and member of the INK4 family of cyclin-dependent kinase (CDK)
inhibitor proteins, and demonstrated that the compound stimulates HSC expansion in murine and human.
Hematopoietic stem cells (HSC) are multipotent adult stem cells that give rise to all the blood cell types
including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes,
megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). However,
broader use of HSC is hindered by the limited number of HSC per harvest. Although HSC expansion can be
achieved by ectopic expression of several positive regulators via retrovirus or lentivirus-mediated methods,
these viral approaches are unfortunately associated with a higher risk of leukemogenesis. Other approaches,
including transgenesis, cytokines, new protein factors, stromal cells, and bioreactors, have also been tested to
expand HSCs, but the specificity for HSCs and the efficacy of these approaches in clinical trials have not been
determined. Indeed, alternative novel approaches for HSC expansion are still in critical need.
We have developed an integrated computational and experimental chemogenomics-based approach for
discovery and development of novel p18-targeted chemical promoters of HSC self-renewal that overcomes the
difficulty of performing costly and time-consuming conventional biochemical studies with adult stem cells that
are extremely rare in tissues. Thus, using our integrated methods2-4, we have discovered the first p18 small
molecule inhibitors (p18SMI) and validated the bioactivities (ED50 = 3.07 μM) by our established in vitro
and in vivo HSC experiments in collaboration with Dr. Tao Cheng, a former faculty at UPCI. We subsequently
confirmed the p18 target specificity by performing the Cobblestone-Area Forming Cell (CAFC) assay using
long-term (LT) cultures of wild type (WT, p18+/+) and knockout (p18-/-) murine mouse bone marrow (mBM) cells.
Importantly, p18 target specificity of p18SMIs was also confirmed by a [-32P] CDK6 bioactivity assay and co-IP
pull down assay. With lead optimization medicinal chemistry synthesis, newly synthesized p18SMIs exhibited
significantly improved HSC expansion bioactivity with ED50 in low nM range. Finally, we confirmed that
p18SMIs promoted expansion of both murine and human HSCs ex vivo by a serial competitive bone marrow
transplantation (cBMT) model, a “gold standard” in vivo functional HSC measurement. Notably, the p18SMIs
did not show significant cytotoxicity toward myeloblast-like 32D cells or primary HSCs, nor did it augment
myeloma cell proliferation. Taken together, our newly discovered p18SMIs represent novel chemical agents for
murine and human HSCs ex vivo expansion and also can be used as valuable chemical probes for further
HSC biology research towards promising utility for therapeutic purposes.
1. Gao Y, Yang P, Shen HM, Yu H, Xie ZJ, Zhang L, Bartlow P, Ji Q, Ding Y, Wang L, Liu H, Ma H, Hao
S, Dong F, Li Y, Zhang P, Cheng H, Liang PH, Miao W, Yuan Y, Cheng T* and Xie XQ* “Smallmolecule inhibitors targeting INK4 protein p18INK4C enhance ex vivo expansion of haematopoietic
stem cells”, Nature Communication, 2015 Feb 18;6:6328. PubMed PMID: 25692908;
2. Xie XQ*, Invited speaker, Nov 2012, "Novel Small Chemical Inhibitors Targeting p18INK4C Protein for
Hematopoietic Stem Cell Expansion”, 3rd International Forum on Stem Cells, Tianjin, China.
3. Yang P., Zhang P., Zhang Y., Wang L., Tong, Q., Cheng T., Gao Y., and Xie X.Q*. “Novel p18INK4C
small molecule inhibitors for hematopoietic stem cell expansion”. ACS 2014 Central Regional
Meeting. Oct, 2014, Pittsburgh, USA
4. Xie XQ* et al, Stem Cell Chemogenomics Knowledgebase, 2013, http://www.cbligand.org/stemcell
3. NOVEL p62ZZ CHEMICAL INHIBITOR WITH THERAPEUTIC POTENTIALS
Xie’s lab was the first to discover and develop p62ZZ chemical inhibitors with promising anti-multiple
myeloma (MM) therapeutic index (Nature Leukemia 2015 in press) in collaboration with Dr. David Roodman.
Actually, emerging studies show that regulatory roles of p62 in protein-protein interactions and autophagy have
recognized p62 as a validated therapeutic target for the treatment of cancer and neurodegenerative
diseases. Our innovation is based on the therapeutic knowledge and our data that the Sequestosome-1 (or
p62) plays critical roles in the survival, growth and metastasis of MM cells. P62 is a key domain activating NFB, and p38 MAPK, both of which are aberrantly activated in MM, thus it is a promising drug target for MM
treatment. We have proved that the ZZ domain of p62 is responsible for increased MM cell growth and
osteoclast (OCL) formation mediated by NF-B and p38 MAPK signaling.
Our discovered lead compound XIE3P62ZZ (#3 or XRK3, 4.31 M) exhibited notable p62 antagonistic
effects and significantly reduced survival of human MM cells and also inhibited osteoclastogenesis (Patent: Xie
et al. PCT/US2012/049911). The specificity was further confirmed by p62-/- experiments, in which effects
of the inhibitor XRK3 on MM cells and tumor necrosis factor (TNF)-α-induced osteoclast (OCL) formation were
lost upon p62-/- gene deficiency. Our preliminary chemistry modification of this lead produced more potent p62
inhibitor analogs (e.g., XIE1-10b: IC50 1.12, XIE1-62a: 0.63 M) with improved drug-like properties (t1/2 = 4.5
hrs, Bioavailability 43%). The in vivo MM xenograft murine model revealed significantly inhibited MM tumor
growth (>75%) and increased mean survival time (53%) compared with the control group. We have also
demonstrated that:  NF-κB and p38 MAPK signaling are increased in primary bone marrow stromal cells from
MM patients;  genetic silencing or deletion of p62 in patient- or mouse-derived stromal cells resulted in a
marked reduction in the capacity of stromal cells to support the growth of MM cells and osteoclastogenesis; 
the p62 ZZ-type zinc finger domain was identified to be the structural basis of p62 to support
osteoclastogenesis and the growth of MM cells.  p62-ZZ domain specificity of XRK3 is confirmed by co-IP pull
down assay. The discovered p62Z chemical inhibitors will be valuable chemical probe for studies of cell
signaling pathways associated with diseases such as multiple myeloma.
1. Xie, X-Q*, Myint, K. Kurihara N, Roodman, D.: “P62-ZZ Chemical Inhibitor for Multiple Myeloma
Intervention” (2012), USSN 61/521,287, PCT/US2012/049911.
2. Teramachi J, Rebecca S, Yang P, Zhao W, Mohammad K, Guo JX, Anderson HL, Zhou D, Feng R,
Myint KZ, Maertz N, Beumer JH, Eiseman, JL, Windle JL, Xie XQ*, Roodman D*, Kurihara N*.
“Blocking the ZZ Domain of Sequestosome1/p62 Suppresses Myeloma Cell Growth and Osteoclast
Formation In Vitro and Induces Dramatic New Bone Formation in Myeloma-Bearing Bones In Vivo”
Leukemia (Nature) 2015 (accepted) (*co-correspondent authors)
3. Teramachi J, Myint KZY, Feng RT, Xie XQ, Windle JJ, Roodman D, Kurihara N. “Blocking the ZZ
Domain of Sequestosome 1/p62 Suppress the Enhancement of Myeloma Cell Growth and Osteoclast
Formation by Marrow Stromal Cells”. Blood, 2011, 118(21):406
4. DESIGN/DISCOVERY OF NOVEL CANNABINOID RECEPTOR CB2 LIGANDS
The cannabinoid receptor CB2 is highly expressed in immune cells and is an important G-protein coupled
receptor (GPCR) for immune signal transduction. Emerging studies in mice and humans suggest an important
role for the endocannabinoid system in autoimmune, inflammation, and immune-origin diseases. Thus,
targeting CB2 receptor is a promising therapeutic strategy for the treatment of these diseases, particularly for
osteoporosis (a bone morphogenetic protein auto-immune disorder), multiple myeloma (MM) (immune B
plasma caused bone disease). Dr. Sean Xie and his team have discovered novel CB2 chemical agents with
promise for treatment of multiple myeloma and osteoporosis diseases. We have designed and synthesized a
series of selective CB2 inverse agonists with novel chemical scaffolds, and top 3 compounds showed excellent
CB2 binding affinity (Ki < 10 nM, selectivity index > 100) and effective anti-osteoporosis and anti-MM
activities. Our innovative CB2 compounds exhibit good drug-like properties with minor toxicity.
1. Four Patents: (1) Xie* X-Q, Chen J, Zhang Y: "Ligands specific for cannabinoid receptor subtype 2".
PCT/US2008/012395; WO 2009/058377; US20110118214 A1. (2) Xie* X-Q, Feng R, Yang P: “Novel
cannabinoid receptor 2 (CB2) inverse agonists and therapeutic potential for multiple myeloma and
osteoporosis bone diseases”. USSN 61/576,041, 2012.
2. Yang P, Myint KZ, Tong Q, Feng R, Cao H, Almehizia AA, Wang L, Bartlow P, Gao Y and Xie XQ*: “Lead
discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2
receptor inverse agonists and osteoclast inhibitors”. J Med Chem 2012, 55(22):9973-9987.
3. Yang P, Wang L, Feng R, Almehizia AA, Tong Q, Myint KZ, Ouyang Q, Alqarni MH, Xie XQ*: “Novel triaryl
sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors:
discovery, optimization, and biological evaluation.” J Med Chem 2013, 56(5):2045-2058.
4. Ouyang Q, Tong Q, Peng RT, Myint KZ, Yang P, Xie XQ*: “Trisubstituted Sulfonamides: A New
Chemotype for Development of Potent and Selective CB2 Receptor Inverse Agonists.” ACS Medicinal
Chemistry Letters 2013, 4(4):387-392.
4. BIOASSAY AND ANIMAL STUDIES OF OSTEOPOROSIS AND BONE DISEASES RELATED
Xie has established innovative computational-chemogenomics-knowledgebase-guided CB2-mediated
signaling mechanism studies and system pharmacology research as well as in vitro osteoclast and in vivo
ovariectomized (OVX) rat osteoporosis model experiments through collaboration with D Roodman and D
Gilson (see their letters). Due to the interactions between myeloma cells and cells of the bone marrow
microenvironment, the osteoporosis (OP) or osteolytic bone disease associated with myeloma is inextricably
linked with tumor progression. High incidence of bone metastasis in MM patients (95-100%) is associated with
severe bone pain and pathological fracture (60%), which has been defined as the result of activated osteoclast
and suppressed osteoblast. With many years of developed research investigations and how-know
technologies, we have found that high levels of expression of active CB2 were observed in human MM cell
lines and primary CD138+ myeloma cells. Our discovered CB2 ligand, phenylacetylamide (PAM, or XIE95),
inhibits MM growth through cell cycle modulation, mitotic death and cytoskeleton disruption. In particular, our
studies show that CB2 gene silencing rescues PAM-induced inhibition of MM cell proliferation. Furthermore, it’s
been reported that CB2 is expressed in osteoclast and osteoblast as well as their precursor cells. CB2-/- mice
showed accelerated age-related trabecular bone loss and cortical expansion. CB2-/- osteoclast number and
trabecular osteoblast activity were increased. The role of CB2 pathway is important in MM-induced bone
remodeling. We found that our compound favorably suppressed osteoclast formation in both murine and
human osteoclastogenesis. Our top CB2 compounds demonstrated promising therapeutic index by animal
efficacy and toxicity laboratory studies.
1. Feng R, Tong Q, Xie Z, Wang L, Lentzsch S, Roodman GD, Xie XQ*: Targeting cannabinoid receptor-2
pathway by phenylacetylamide suppresses the proliferation of human myeloma cells through mitotic
dysregulation and cytoskeleton disruption. Mol Carcinog 2015:PMID: 25640641
2. Feng RT, Milcarek CA, Xie XQ*: Antagonism of cannabinoid receptor 2 pathway suppresses IL-6induced immunoglobulin IgM secretion. BMC Pharmacol Toxico 2014, 15:30 PMID:24913620.
3. Gertsch, J.; Leonti, M.; RadunerS.; RaczI.; Chen, J.-Z.; Xie, X.-Q.; Altmann, K.; Zimmer, A.; Karsak, M.
Beta-Caryophyllene is a Dietary Cannabinoid. PNAS 105(2008), 9099-9104.
D. Research Support:
Ongoing Research Support
NIH R01 DA025612
(Xie, PI)
04/10/10- 03/31/16 (no costs extension)
2.40 Calendar
Structure and Function of CB2 Ligand and G-protein Recognition Pockets
This project is to focus on characterize the cannabinoid receptor subtype 2 (CB2) binding residues and
functional domains and then to elucidate 3D structures of the recognition pockets important to
agonist/antagonist binding and G-protein coupling by combined biophysical and biochemical approaches.
NIDA P30 PDA035778A
(Xie, PI/Director) 07/01/2014-06/30/19
2.4 Calendar
NIDA Core “Center of Excellence” grant program
The overall goal of the Computational Drug Abuse Research (CDAR) Center is to advance state-of-the art
computational chemical genomics technologies for research toward the prevention and treatment of drug
abuse (DA) and neurological disorder diseases. This is a joint initiative under University of Pittsburgh and
Carnegie Mellow University.
Completed:
NIH R21 HL109654
(Xie, PI)
07/01/2011-06/30/14
1.20 Calendar
Screen and Design p18 Chemical Probes for Hematopoietic Stem Cell Self-Renewal
This project is to screen/design small drug molecules targeting CKI p18, and use them as chemical probes to
explore the mechanisms of activating HSC self-renewal in increasing the quantity of functional stem cells.
Ultimately, our work is to developing HSC drugs for therapeutic uses.
NIH P50 GM067082
(Xie, co-PI and Core Co-Director)
09/01/08-08/31/14 0.60 Calendar
New Concepts, Methodologies and Scaffolds for Diversity-Oriented Organic Synthesis (Wipf)
This project is to build a Pitt Center for Chemical Methodologies and Library Development (PCMLD). We will
carry out the planned computational chemistry and computational biology project defined in UP-CMLD.
NIH NCI/SAIC 29XS127 Task Order 6 (Xie, co-PI, Core Director) 09/01/08-08/31/13
0.60 Calendar
Chemical Biology Consortium – University of Pittsburgh Chemical Diversity Center (UPCDC) (Huryn)
The goal of this project is to identify and optimize inhibitors of STAT3 activation for use as potential drugs for
the treatment of squamous cell carcinoma cancers of the Head and Neck.
NIH NLM/R01DA015417
P.I.: X.-Q. Xie,
09/1/05-08/30/08
A Public Cannabinoid Molecular Information Database Repository System
This project is to develop a public cannabinoid (CB) molecular information database (CBID) repository
system to facilitate data sharing and enhance information exchange among the research communities
and beyond.
NIH U54 MH074411 (Dr. John S. Lazo, P.I.)
NIH Roadmap Initiative
Co-P.I.: X.-Q. Xie,
07/1/05-06/30/08
NIH Roadmap Initiative grant to build “Pittsburgh Molecular Libraries Screening Center”
NIH R01 DA015770
P.I.: X.-Q. Xie
02/01/2003-01/31/2006
Advanced Isotope Aided NMR for GPCR CB2 Structural Study
The objective is to develop a novel approach to overexpress/purify the recombinant CB2 protein fragments
in isotope-enriched E. coli/M9 media for 3D NMR structural biology studies.
NIH R29 DA011510
P.I.: X.-Q. Xie
Integrated NMR and Computer Modeling for CB Ligand Design
02/01/1998 – 01/31/2003