AGENDA
ACPHS Sixth Annual Research Forum
Saturday, January 23, 2016
Albany Campus, Gozzo Student Center, Room 201
Vermont Campus, Room 310
8:00 – 8:30
Continental Breakfast
8:30 – 8:40
Welcome Message
ACPHS President Greg Dewey, PhD
8:40 – 9:15
Keynote Speaker
James A. Dias, PhD
Vice President for Research and Professor, Dept. of Biomedical Sciences
University at Albany (SUNY)
Exploiting Biased Signaling of Follitropin Receptor as a Therapeutic Strategy for
the Continuum of Women’s Reproductive Health
9:15 – 9:30
Safety First
Michele Shepard, PhD
Colden Corporation, Ballston Lake, NY
1
AGENDA
9:30 – 9:40
Recognition of Faculty and Staff Services
to Office of Research and Scholarly Activity
Shaker A. Mousa, PhD, MBA
ACPHS Vice Provost of Research
Professor, Dept. of Pharmaceutical Sciences
Executive Vice President and Chairman, PRI
9:40 – 9:50
ACPHS Chapter AAPS
Lilly Cheng (President)
Steven Lane (Past President)
AAPS at ACPHS: Promoting Pharmaceutical Science through
Student Research and Community Outreach
Panel Discussion
Oncology
9:50 – 11:00
Moderator: Shaker A. Mousa
Panel: Dhruba Bharali, Allison Burton-Chase, Paul J. Davis, Tamer Fandy, Karen C. Glass,
Vandhana Muralidharan-Chari, Thomas O’Grady, Tarun Patel
I.
II.
III.
IV.
11:00 – 11:45
Molecular mechanisms in cancer: Muralidharan-Chari, Patel
Epigenetics in cancer: Fandy, Glass
Nanobiotechnology and impact on translational research in cancer: Bharali, Davis
Behavioral and health outcomes approaches to cancer epidemiology: Burton-Chase,
O’Grady
POSTER VIEWING & Networking
2
AGENDA
11:45 – 12:20
Featured Speaker
Shahrokh (Steve) Falati, PhD, Esq.
Managing Partner
Falati International Law Firm, Albany, NY
Patenting Innovative Ideas in the Life Sciences
12:20 – 2:30
Oral Session
LUNCH and POSTER VIEWING
Target Identification
2:30 – 3:00
Timothy J. LaRocca, PhD
ACPHS Assistant Professor, Dept. of Basic & Social Sciences
Hyperglycemia Primes Cells for Necroptosis
Noureldien H. E. Darwish, MD
Visiting PhD student at PRI, & Faculty of Medicine, Mansoura University, Mansoura, Egypt
Acute Myeloid Leukemia Stem Cell Markers in Prognosis and Targeted Therapy
3
AGENDA
Oral Session...continued
Yana Cen, PhD
ACPHS Assistant Professor, Dept. of Pharmaceutical Sciences
Chemical Biology Approach for Sirtuin Profiling
3:00 – 3:10
Announcement of the Blythe Award
3:10
Closing Remarks
Greg Dewey
4
KEYNOTE SPEAKER
KEYNOTE
Exploiting Biased Signaling of Follitropin Receptor as a Therapeutic
Strategy for the Continuum of Women’s Reproductive Health
James A. Dias, PhD
Vice President for Research and Professor, Department of Biomedical Sciences
University at Albany, State University of New York, Albany, NY
Follicle stimulating hormone (FSH, follitropin) is a pituitary derived heterodimeric glycoprotein gonadotropin which is
an essential regulator of ovarian follicle growth and hence oogenesis in women, and is also involved in high quality
spermatogenesis in males. Female mice null for FSH beta subunit as well as female FSH receptor (FSHR) knockout mice
are infertile. FSH drives estrogen synthesis in females, and elevation of estrogen during the menstrual cycle suppresses
FSH production. This feedback loop was exploited to develop estrogen based orally active contraceptives, albeit with
adverse side effects. Mutation of FSHR in humans can lead to female infertility, establishing FSHR as an important target
for contraceptive development and potentially providing alternative to estrogen based contraceptives. The crystal
structure and structure activity relationships of FSH has been well studied as a prelude to developing better therapeutic
versions of FSH for fertility therapy, as well as to understand how to ablate the hormone receptor interaction towards
development of an FSHR based contraceptive. In addition the crystal structure of the FSHR extracellular binding domain
has been determined, providing further critical information about the binding interface. The FSHR is comprised of a large
rigid leucine rich repeat extracellular domain and the crystal structures of FSH bound to FSHR revealed an extensive
contact area between the ligand and receptor. Thus these data suggested that development of a small molecule
contraceptive antagonist or an FSH mimic agonist would be a challenge if the target were the FSHR large extracellular
domain. Since many drugs used today are based on GPCR transmembrane domain (TMD) targets and because FSHR is
a G-protein coupled receptor (GPCR) with a prototypical TMD, development of a small molecule modulator targeting
FSHR seemed possible. Addex Therapeutics (Geneva) developed small molecule negative allosteric modulators (NAM)
of FSHR. The first of this series tested (ADX61623) revealed some remarkable insights into FSHR cellular physiology.
For example, although ADX61623 blocked FSH induced cAMP production, FSH binding was unaffected, and illustrating
that hormone binding to the extracellular domain of FSHR is necessary but not sufficient to engender a cellular response.
Not unexpectedly, progesterone production, a cAMP driven steroidogenic response was completely inhibited when rat
granulosa cells were treated with FSH in the presence of ADX61623. An unanticipated observation was that ADX61623
did not block FSH induced estradiol production but rather increased FSH induced estradiol production which is
considered a canonical downstream cAMP/PKA pathway endpoint. This serendipitous observation shed light on the fact
that the FSHR exhibits biased signaling, the first such demonstration for any of the pituitary glycoprotein hormone
receptors. In addition, those results suggested that ADX61623 may be useful in women as a non-estrogen based
therapeutic during the perimenopausal period when ovarian estrogen production is waning, and ADX61623 may enhance
ovarian estrogen production. ADX61623 only partially suppressed oogenesis in vivo, in an immature rat bioassay for
FSH and so additional FSH NAMs were developed for further testing as a contraceptive. ADX68692 was similarly tested
in cell bioassays and revealed similar characteristics to ADX61623 with one important difference: estradiol production
was suppressed. Further, when tested in vivo, ADX68692 suppressed FSH mediated oogenesis in an immature rat
bioassay for FSH. These results demonstrated that suppression of estradiol production is critical to the contraceptive
effect of this FSHR NAM. In summary, FSHR biased signaling provides opportunities for nuanced small molecule
development that can on the one hand act as a contraceptive, while on the other hand ameliorate perimenopausal
symptoms. Biased antagonism of FSHR, and development of non-steroidal contraception seems to require that both arms
of the FSHR steroidogenic pathway must be effectively blocked to control fertility and in particular, estrogen
biosynthesis. In addition it seems reasonable to propose that estrogen dependent diseases such as endometriosis may
benefit from inhibition of FSHR cAMP independent signaling at the ovary using an FSHR NAM approach. (Supported
by NIH HD18407 and Addex Therapeutics).
5
AAPS
AAPS at ACPHS: Promoting Pharmaceutical Science
through Student Research and Community Outreach
Hui (Lilly) Cheng, Current President
Steven Lane, Past President
Albany College of Pharmacy and Health Sciences, Albany, NY
The American Association of Pharmaceutical Scientists (AAPS) is an international professional
organization that promotes advancements in pharmaceutical science. Since its establishment in
1986, it has fostered collaboration between academia and industrial laboratories with the goal of
facilitating innovations that improve global health.
Our student run chapter here at ACPHS, founded in 2010, has sought to establish these same ideals
in our own community and on campus. We host industry guests, organize field trips to locations
of interest, and participate in community outreach events throughout each semester. Through
Research Happy Hour events (RHHs) and our lab connection newsletter, we bring together
aspiring student scientists and research faculty to facilitate student placement and promote campus
research.
If you wish to join our efforts in promoting scientific inquiry or are interested in recruiting and/or
mentoring a student in your research lab, please email us at aaps@acphs.edu
Faculty advisor: Haian (Andy) Zheng
6
ONCOLOGY PANEL
Oncology Panel
Hypoxia and Tumor Biology
Tarun Patel, Provost and Vice President of Academic Affairs
Albany College of Pharmacy and Health Sciences, Albany, NY
Some years ago, the thinking was that if tumors are deprived of a blood supply by inhibiting
angiogenesis (blood vessel proliferation), one could “starve” the tumors of oxygen (hypoxia) and
nutrients and kill them. While this may be true, it was discovered that tumors can survive hypoxia
(low oxygen) and adapt to hypoxic conditions. The key regulators of tumor growth in hypoxia are
hypoxia inducible factors (HIFs) whose levels are elevated because their degradation in hypoxia
is attenuated. These HIFs (three in total) are transcription factors and two of the best studied (HIF1
and HIF2) upregulate the expression of genes that change the aerobic metabolism of cells to adapt
to the hypoxic condition. Essentially, they do this by altering the expression of glucose transporter
and glycolytic enzyme genes to increase glycolysis and decrease mitochondrial oxygen-dependent
metabolism. A number of proteins regulate the levels of HIF1 and HIF2 proteins. One example is
the Sprouty family of proteins. The Sprouty proteins (4 in total) inhibit cellular proliferation and
cell migration. They play a very important role in normal tissue development as well as growth
and proliferation of tumors. Sprouty2 has been shown to be decreased in tumors of the breast, liver,
lung, and prostate. Using Sprouty2 as a prototype of its family member, we have discovered two
novel mechanism by which Sprouty2 decreases HIF1 and HIF2 and, therefore, biological
processes regulated by HIFs such as glucose uptake. The discussion will therefore focus on how
tumors adapt to hypoxia and whether targeting of HIFs present as possible modalities toward the
treatment of cancers.
7
ONCOLOGY PANEL
Oncology Panel
Microvesicles Facilitate Drug Resistance in
Pancreatic Cancer Cells by Removal of
Chemotherapeutic Drugs
1*
Vandhana Muralidharan-Chari, 2Hamed Gilzad Kohan,
3
Alexandros G. Asimakopoulos, 1Thangirala Sudha,
3
Stewart Sell, 3Kurunthachalam Kannan, 4Mehdi Boroujerdi,
1
Shaker A. Mousa
V. M-Chari
1
The Pharmaceutical Research Institute
Albany College of Pharmacy and Health Sciences, Rensselaer, NY
2
Department of Pharmaceutical Sciences
Albany College of Pharmacy and Health Sciences, Albany, NY
3
Wadsworth Center, New York State Department of Health,
and School of Public Health, University at Albany, Albany, NY
4
School of Pharmacy and Pharmaceutical Sciences
University of Massachusetts, Lowell, MA
High mortality in pancreatic cancer patients is partly due to cancer cells’ ability to resist
chemotherapy. This study provides evidence that cancer cells utilize microvesicles to gain drug
resistance. Using a panel of pancreatic cancer cell lines with varying degrees of sensitivity to
gemcitabine, we show that gemcitabine treatment triggers the cells to release microvesicles at an
amount that is directly proportional to their sensitivity to gemcitabine. Inhibiting the release of
microvesicles sensitized the pancreatic cancer cells to gemcitabine treatment both in vitro and in
vivo. We identified the mechanism by which microvesicles enable drug resistance in pancreatic
cancer cells and this will be discussed in the context of drug-resistant and drug-sensitive pancreatic
cancer cells. These findings document a role for microvesicles in the removal of chemotherapeutic
drugs and provide translational evidence demonstrating that inhibiting the release of microvesicles
can sensitize drug-resistant cancer cells to conventional therapies.
8
ONCOLOGY PANEL
Oncology Panel
Quantitative Comparison of the DNA
Methylation Reversal Activity of DNA
Hypomethylating Agents
Phillip Smith and Tamer Fandy
T. Fandy
Department of Pharmaceutical Sciences
Albany College of Pharmacy and Health Sciences, Colchester, VT
Purpose: The role of DNA hypomethylating agents as antitumor agents is well established. These
agents are very diverse in terms of origin, cytotoxicity and pharmacological activity. The potency
of these compounds as hypomethylating agents was never compared using a standard assay and
was never correlated to their antitumor activity. The purpose of this study is to compare the potency
of these compounds in reversing DNA methylation using DNA pyrosequencing.
Methods: Eight DNA hypomethylating agents were chosen to compare their activity in leukemia
cells by DNA pyrosequencing. These agents are decitabine, 5-azacytidine, SGI-110, zebularine,
RG-108, 6-thioguanine and the phytochemicals EGCG and PEITC. Gene specific methylation
reversal using primers for p15 and CDH-1 genes and LINE-1 methylation reversal as a surrogate
marker for global DNA methylation were used to quantitatively compare DNA methylation
reversal by these compounds.
Results: The methylation reversal activity of the eight compounds was highly variable. The
cytosine analogues decitabine, 5-azacytidine, SGI-110 and zebularine were the only agents that
demonstrated a dose-dependent methylation reversal. The second generation hypomethylating
agent SGI-110 did not show significant increase in methylation reversal compared to the less
metabolically stable decitabine at equimolar doses. The activity of the specific DNMT-1 inhibitor
RG-108 was significantly less than the cytosine analogues. Finally, the phytochemicals EGCG and
PEITC were the least active and required the use of very high concentrations to induce minimal
reversal of DNA methylation.
Conclusion: The cytosine analogues are the most potent DNA hypomethylating agents. The
comparable activity of the highly stable SGI-110 to its less stable analogue decitabine is intriguing
and questions the hypothetical superiority of SGI-110 over decitabine.
9
ONCOLOGY PANEL
Oncology Panel
Histone Recognition by the ING3 PHD Finger in
the TIP60 Histone Acetyltransferase Complex
1
Sophia Kim, 1Senthil Natesan, 2Gabriel Cornilescu,
1
Samuel Carlson, 2Marco Tonelli, 3Urszula L. McClurg,
3
Olivier Binda, 2John L. Markley, 1Stefan Balaz and
1
Karen C. Glass
K. Glass
1
Department of Pharmaceutical Sciences,
Albany College of Pharmacy and Health Sciences, Colchester, VT
2
National Magnetic Resonance Facility at Madison and Department of Biochemistry
University of Wisconsin-Madison, Madison, WI
3
Newcastle Cancer Centre at the Northern Institute for Cancer Research
Newcastle University, Newcastle upon Tyne, United Kingdom
Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer
development. One molecular mechanism that regulates access to genetic information includes
recognition of histone modifications, which is carried out by protein modules that interact with
chromatin and recruit enzymatic complexes to regulate gene expression. The ING3 tumor
suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via
recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated
in various human cancers. However, the molecular mechanisms targeting ING3 to histones, and
the role of this interaction in the cell remain elusive. We examined the molecular interactions of
the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3 using biochemical
and structural biology approaches. Binding affinities of the ING3PHD with unmodified, mono-, diand tri-methylated histone H3 peptides were determined ITC. NMR titration experiments and
molecular dynamic simulations of the ING3PHD-H3K4me3 interaction coupled with mutagenesis
identified residues essential for histone recognition. Finally, the biological relevance of ING3PHDH3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3mediated DNA damage-dependent cell death. Together, our results reveal the molecular
mechanism of H3K4me3 selection by the ING3PHD, and suggest that this interaction is important
for mediating ING3 tumor suppressive activities.
10
ONCOLOGY PANEL
Oncology Panel
Nano-diamino-tetrac (N-DAT), Effective αvβ3Targeting and Anti-cancer: From the Bench to the
Bedside
Paul J. Davis, Dhruba J. Bharali, Thangirala Sudha,
Murat Yalcin, Shaker A. Mousa
P. J. Davis
The Pharmaceutical Research Institute
Albany College of Pharmacy and Health Sciences, Rensselaer, NY
We previously identified a receptor for tetraiodothyroacetic acid (tetrac) on plasma membrane integrin
αvβ3. The integrin is generously expressed on cancer cells and rapidly dividing blood vessel cells. Acting
via this receptor, tetrac disrupts cell cycle control in cancer cells, induces apoptosis, and is anti-angiogenic.
We have reformulated tetrac by covalently binding it to a nanoparticle (nano-diamino-tetrac, or N-DAT)
so that the agent acts exclusively at the integrin and does not gain access to the cell interior. N-DAT has
potent anti-proliferative actions against a variety of human cancer xenografts in the nude mouse: pancreas,
kidney, brain (glioblastoma), prostate, chemo-resistant breast, and various thyroid cancers. Expression of
a variety of differentially regulated cancer cell survival genes is coherently disrupted by nanotetrac. The
agent inhibits activities of VEGF, bFGF, and EGF, whose receptors engage in crosstalk with the integrin.
Although N-DAT acts at a single cancer cell and blood vessel cell target on the cell surface, it has,
downstream of the tetrac receptor, extensive and desirable actions on cancer cell biology and cancerrelevant angiogenesis. The agent’s toxicology profile determined by us is favorable. Except for contract
toxicology, the preclinical phase of drug development, including scale-up of N-DAT synthesis, is
completed. Tetrac is a naturally occurring inhibitor of the binding of agonist thyroid hormones—Lthyroxine (T4) and 3, 5, 3’-triiodo-L-thyronine (T3)—at the αvβ3 hormone receptor. We have shown that
tetrac has a spectrum of actions at the integrin that are independent of the presence of T 4 and T3. These
actions include 1) inhibition of the pro-angiogenesis activities of vascular growth factors cited above,
apparently by disrupting crosstalk between integrin αvβ3 and nearby vascular growth factor receptors; 2)
disruption of cyclin gene expression, inhibition of anti-apoptotic gene expression and stimulation of
expression of pro-apoptotic genes and of thrombospondin 1, an endogenous inhibitor of angiogenesis. We
have covalently bound tetrac to a 250 nm nanoparticle to limit the activity of tetrac to αvβ3 and to prevent
its access to the intracellular space. Tetrac nanoparticle has been uniformly effective against a variety of
human cancer xenografts in mice and in the chick chorioallantoic membrane. Xenografts include lung,
pancreas, brain (glioblastoma), kidney, prostate and breast. Toxicology in rodents of systemically
administered N-DAT in doses up to 100-fold of those proposed for human subjects has revealed no
changes in weight gain or food intake in treated animals and no histopathological changes after 3 weeks
in heart, brain, liver, and kidney. Preclinical development of N-DAT is essentially complete. Next steps
in drug development are 1) contract toxicology by an agency with FDA experience, and 2) post-toxicology
filing of an investigative new drug (IND) application for FDA Phase I- and early Phase II-testing in cancer
patients with glioblastoma and pancreatic cancer.
11
ONCOLOGY PANEL
Oncology Panel
Nano-synthesis and Assembly of
Various Platforms in Oncology
Dhruba J. Bharali and Shaker A. Mousa
Pharmaceutical Research Institute
Albany College of Pharmacy and Health Sciences, Rensselaer, NY
D. J. Bharali
Nanotechnology profoundly impacts every aspect of modern life. In recent years the biomedical
application of this cutting-edge technology has been used as drug delivery carriers, medical
imaging systems, and biosensors. It is growing exponentially by taking advantage of the unique
physicochemical properties of submicron-sized nanomaterials, and there are some
nanotechnology-based drugs on the market. The unique advantage of the nano-carrier is that it can
be used as a delivery vehicle for a wide variety of active materials (e.g. of water insoluble/soluble
drugs) with different physicochemical properties. The unique multifunctional characteristics and
surface tunable properties of nanoparticles allow them to incorporate multiple entities for targeted
delivery. We will summarize recent nanotechnology advancements in our laboratory as drug
delivery carriers and imaging probes for different diseases, with special emphasis in oncology.
12
ONCOLOGY PANEL
Oncology Panel
Care Coordination and its Impact on Provider
Satisfaction in Lynch Syndrome Survivors and
Previvors
A. M. Burton-Chase
1
Kelsey Hennig, 1Alec LeBorgne, 1Rebecca Chu,
1
Wendy M. Parker, 2Lisa M. Campo-Engelstein, 1Allison M. BurtonChase
1
Department of Basic and Social Sciences, Albany College of Pharmacy and
Health Sciences, Albany, NY
2
Alden March Bioethics Institute, Albany Medical College, Albany, NY
Background: Lynch syndrome (LS) is an inherited cancer syndrome characterized by a predisposition to
several early onset cancers, including colorectal and endometrial cancer. LS involves a complex medical
management regimen that is not well understood by many health care providers (HCP); this lack of
understanding has been associated with lower levels of provider satisfaction when compared to individuals
with sporadic cancer. Additionally, an unsatisfactory patient-provider relationship has been associated with
decreased adherence to screening and surveillance recommendations.
Methods: This study used mixed methodology (online survey followed by a telephone interview) to assess
individuals with LS on factors associated HCP satisfaction and how these factors impact adherence to
screening and surveillance recommendations. LS patients were asked to discuss their transitions in care,
including the HCP involved in their diagnosis, treatment, and survivorship care, the specialty areas of these
HCP, the location of their cancer treatment and survivorship care, and the HCP involved with their ongoing
screening and surveillance. Additionally, patients assessed the qualities of the patient-provider relationship
that are associated with satisfaction and how satisfaction impacts screening and surveillance adherence.
Results: The sample included 57 LS survivors and previvors (mean age of 44 years, range of 21-68).
Participants reported a median of 4 HCP involved in their LS-associated care, with a range of 1-16. The most
commonly reported medical specialties were: 1) gastroenterologist, 2) oncologist, 3) obstetrics-gynecologist,
4) surgeon, and 5) primary care provider. Across multiple measures of provider satisfaction, about 15-20%
of LS survivors and previvors reported low levels of satisfaction with the care they were receiving. Followup interview data indicated that the primary predictor of provider satisfaction is care coordination, although
that concept has multiple meanings. Participants used this concept to refer to communication with their HCP
between appointments, communication between multiple providers, and having one person who is the
primary provider overseeing all of their LS care.
Conclusions: LS patients identify multiple providers as being involved in their LS care; however there
appears to be a lack of coordination between these providers, which is leading to lower provider satisfaction
and, ultimately, decreased adherence to appropriate screening and surveillance. It also appears that provider
satisfaction may be more about quality of care than face-to-face time with their HCP. Given these findings,
interventions should be developed to improve care coordination in the LS population.
13
ONCOLOGY PANEL
Oncology Panel
Thyroid Cancer Incidence Attributable to
Overdiagnosis in the United States 1981-2011
T. O’Grady
Thomas J. O’Grady, 2,3Margaret A. Gates, 2,4Francis P.
Boscoe
1,2
1
Department of Basic and Social Sciences
Albany College of Pharmacy and Health Sciences, Albany, NY
2
School of Public Health
University at Albany, Rensselaer, NY
3
Bureau of Chronic Disease Evaluation and Research
New York State Department of Health, Albany, NY
4
Bureau of Cancer Epidemiology
New York State Department of Health, Menands, NY
Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for
both men and women of all ages and races. Overdiagnosis is partially responsible for this trend,
though its magnitude is uncertain. This study examines papillary thyroid cancer incidence
according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are
attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer
incidence, 1981 to 2011, using the Surveillance, Epidemiology, and End Results (SEER) national
cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated.
We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis
in 2011 was 5.5% and 45.5% in men ages 20-49 and 50+, and 41.1% and 60.1% in women ages
20-49 and 50+ respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary
thyroid cancers that likely would never have caused any clinical symptoms. The detection of earlystage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part
due to overdiagnosis. Further studies into the prevention, risk stratification, and optimal treatment
of papillary thyroid cancer are warranted in response to these trends.
14
FEATURED SPEAKER
FEATURED
Patenting Innovative Ideas in the Life Sciences
Shahrokh Falati, Ph.D., Esq.
Managing Partner, F A L A T I, Albany, NY
We are seeing that the life sciences industry is taking over from the tech sector in driving global
innovation, according to a Thomson Reuters analysis of global patents. More patents were applied
for or granted last year than in any other year in history, indicating that humankind has never been
more inventive. One area of continued interest is protecting innovations occurring in the
Biotechnology or Life Sciences industry. This talk will give an overview and delve deeper into
particular Intellectual Property legal issues facing stakeholders in this industry.
15
ORAL SESSION
Oral Session
Chemical Biology Approach for Sirtuin Profiling
1
Elysian Graham, 1Marci Wood, 1Stacia Rymarchyk,
2
Kangling Zhang, 3Hening Lin, 1Yana Cen
Y. Cen
1
Department of Pharmaceutical Sciences
Albany College of Pharmacy and Health Sciences, Colchester, VT
2
Department of Pharmacology and Toxicology,
University of Texas Medical Branch, Galveston, TX
3
Department of Chemistry and Chemical Biology, Baker Laboratory,
Cornell University, Ithaca, NY
Ever since being discovered two decades ago, the research on sirtuins has been growing
exponentially. This unique class of enzymes has been implied as “longevity gene”, and is thought
to mediate the beneficial effect of low calorie intake. Although being pursued intensively as
therapeutic target, the connections between sirtuin activity and disease development remain
unclear. Our study aims to engineer novel chemical tools to monitor the functions of sirtuins in
native biological environment. These chemical probes and labeling strategies will provide
transformative technology to allow the direct linking of sirtuin activity to distinct physiological
processes.
The design of the chemical tools is based on the mechanism of sirtuin’s action, mimicking how
the enzyme would promote chemical transformation. These probes will first be tested on purified
sirtuin enzymes, or a mixture of enzymes containing sirtuins. They are expected to directly report
the fraction of active sirtuins. We believe some of these probes can get into the cells and interact
with sirtuins in their native environment. This would allow us to visualize sirtuin’s action inside
the cells directly.
The successful development and application of these chemical tools will reveal how exactly the
sirtuins act in cells to elicit cardioprotective effects. These probes will directly attribute certain
pathological change to sirtuin activity. They will also provide platforms for the discovery of
sirtuin-targeted therapeutics.
16
ORAL SESSION
Oral Session
Hyperglycemia Primes Cells for Necroptosis
1
Timothy J. LaRocca, 2Sergey Sosunov, 1Nicole Flaherty,
2
Vadim Ten, and 3Adam J. Ratner
T. J. LaRocca
1
Department of Basic and Social Sciences, Albany College of Pharmacy
and Health Sciences
2
3
Department of Pediatrics, Columbia University
Departments of Pediatrics and Microbiology, New York University
Programmed cell death (PCD) is critical to the pathology of many mammalian diseases. While
apoptosis is the best studied PCD, other forms of PCD have emerged including programmed
necrosis (necroptosis). Necroptosis is primarily induced by inflammatory cytokines of the TNF
family, most notably TNF-α, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand
(TRAIL). As necroptosis is induced during inflammation it has been shown to be critical to septic
shock, ischemia-reperfusion injury, and neurodegeneration. Following induction, necroptosis is
controlled by phosphorylation of RIP1 kinase coinciding with formation of a cytosolic complex
called the necrosome. Two necrosome components, RIP3 kinase and mixed lineage kinase-like
(MLKL) protein, become activated in this complex and mediate downstream effector mechanisms
of necroptosis including reactive oxygen species (ROS) formation by mitochondria and glycolytic
formation of advanced glycation end products (AGEs). Glucose is critical in driving these effector
pathways as two products of glycolysis, pyruvate and methylglyoxal, are needed for mitochondrial
ROS formation and AGE formation, respectively. Therefore, we hypothesized that conditions of
excess glucose (hyperglycemia) may prime cells for death via necroptosis. Our results show that
necroptosis of red blood cells (RBCs) induced by CD59-specific bacterial pore-forming toxins is
primed by hyperglycemic conditions in vitro. The basis of this priming was due to increased
glycolytic formation of AGEs. Importantly, we show that two models of nucleated cell necroptosis,
TNF-induced necroptosis of U937 macrophages and FasL-induced necroptosis of Jurkat T cells,
are significantly primed for this cell death in hyperglycemic conditions. Formation of ROS and
AGEs contributed to hyperglycemic priming of necroptosis in these cells; however, there were
also significantly higher amounts of RIP1, RIP3, and MLKL in hyperglycemic conditions,
providing an alternative explanation for the priming of necroptosis in nucleated cells.
Hyperglycemic priming of cell death was specific to necroptosis as extrinsic apoptosis and
eryptosis (another form of PCD in RBCs) were not primed by excess glucose. Interestingly,
ischemia-reperfusion injury of the brain (which is driven by necroptosis) is enhanced during
hyperglycemia in vivo as measured by infarct size. Increased infarcts in hyperglycemic mice were
completely prevented if necroptosis was halted by an inhibitor of RIP1. This preliminary work
forms the foundation of a project that will explore the relevance of necroptosis to diabetes, which
is associated with increased incidence of inflammation and infection.
17
ORAL SESSION
Oral Session
Acute Myeloid Leukemia Stem Cell Markers in
Prognosis and Targeted Therapy: Potential
Impact of BMI-1, TIM-3 and CLL-1
1,2
N. H. E. Darwish
Noureldien H. E. Darwish, 2Sudha Thangirala,
2
Kavitha Godugu, 1Osama E. Elagroudy, 1Hasan A.
Abdelghaffar, 1Emad E. A. Hassan, and 2Shaker A. Mousa
1
Faculty of Medicine,
Mansoura University, Mansoura, Egypt
2
The Pharmaceutical Research Institute
Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional
chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and
drug resistance. LSCs might rely on the B-cell-specific moloney murine leukemia virus integration
site-1 (BMI-1) in promoting cellular proliferation and survival. Growth of LSCs in
microenvironments that are deprived of nutrients leads to up-regulation of the signaling pathways
during the progression of the disease, which may illustrate the sensitivity of LSCs to inhibitors of
those signaling pathway as compared to normal cells. In this study, we analyzed the expression of
LSCs markers (CD34, CLL-1, TIM-3 and BMI-1) using quantitative RT-PCR in bone marrow
samples of 40 AML patients of different FAB types (M1, M2, M3, M4, M5, and M7). The
overexpression of TIM-3, CLL-1, and BMI-1 was markedly correlated with poor prognosis in
these patients. We studied also the expression of these markers in 2 AML cell lines (Kasumi-1 and
KG1-a) using flow cytometry and quantitative RT-PCR. Our in vitro findings demonstrate that
targeting BMI-1, which markedly increased in the leukemic cells, was associated with marked
decrease in leukemic burden. This study also presents results for blocking LSCs’ surface markers
CD44, CLL-1, and TIM-3. These markers may play an important role in elimination of AML. Our
study indicates a correlation between the expression of these markers and the aggressiveness of
AML and thus the potential impact of prognosis and therapies that target LSCs on improving the
cure rates.
18
POSTERS
Levofloxacin-associated Tendinopathy: What is the Risk?
Monique R. Bidell and Thomas P. Lodise
Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY
Comparative Anti-Inflammation and Anticoagulation Activity among Heparin Sources
Donniecia Corke, Jaehan Kim, Vandhana Muralidharan-Chari, Shaker A. Mousa
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Effects of Antioxidant and αvβ3 Integrin Antagonists on Gemcitabine-induced NF-κB in HeLa Cells
Melis Debreli Coskun and Shaker A. Mousa
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Effects of Antioxidants and αvβ3 Integrin Antagonists on NF-κB Induction in Human Monocytic Cells
Melis Debreli Coskun and Shaker A. Mousa
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Development of Tumor Targeted Irradiation Protocol in a Small Animal Cancer Model using Faxitron
X-ray Unit
1
Mahboob UR Rehman, 2Noureldien HE Darwish, 1Lubna Peerzada, 2Melis Debreli Coskun, 3Jahangir Satti,
2
Thangirala Sudha and 2Shaker A. Mousa
1
University at Albany, SUNY, Albany, NY; 2Pharmaceutical Research Institute, Albany College of Pharmacy
and Health Sciences, Rensselaer, NY; 3Albany Medical Center, Albany, NY
Acute Myeloid Leukemia Stem Cell Markers in Prognosis and Targeted Therapy: Potential Impact of
BMI-1, TIM-3 and CLL-1
1,2
Noureldien H. E. Darwish, 2Sudha Thangirala, 2Kavitha Godugu, 1Osama E. Elagroudy, 1Hasan A.
Abdelghaffar, 1Emad E. A. Hassan, and 2Shaker A. Mousa
1
Faculty of Medicine, Mansoura University, Mansoura, Egypt; 2Pharmaceutical Research Institute, Albany
College of Pharmacy and Health Sciences, Rensselaer, NY
Medicalization versus Demedicalization: The Question of Resistance
Barry DeCoster
Department of Humanities and Communication
Albany College of Pharmacy and Health Sciences, Albany, NY
Preventive Screening and Risk for Women with Lynch Syndrome: Initial Results of a Case Control Study
Wendy M. Parker, Kirsten M. Donato, Allison M. Burton-Chase
Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY
Synthesis of Chitosan Glycyrrhetinic Acid Nanoparticles as a Targeted Nano Carrier for EGCG to
Hepatocyte
1,2
Mostafa H. Elberry, 1Weikun Li, 1Shaker A. Mousa
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY;
2
National Cancer Institute, Cairo University, Cairo, Egypt
19
POSTERS
Interprofessional Education (IPE): Students from Eight Healthcare Disciplines Working Together via
Video Conferencing
1
Charlotte Fielding, 1Bobby Ciau, 1Kathleen Boland, 2Mary Val Palumbo
1
Albany College of Pharmacy & Health Sciences, Albany, NY; 2University of Vermont, Burlington, VT
Using Isothermal Calorimetry to Determine ATAD2b to Histone Binding Affinities
Jamie C. Gay, Samuel Carlson, and Karen C. Glass
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT
Design and Synthesis of Activity-based Chemical Probes for Specific Sirtuin Isoforms
Elysian Graham, Stacia Rymarchyk, Yana Cen
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT
Synthesis and Evaluation of Co-Drugs Derived from Methotrexate and Ibuprofen
Martha A. Hass, Siji Thomas, Shriya Mathur
Albany College of Pharmacy and Health Sciences, Albany, NY
Thymoquinone Modulates Blood Coagulation in vitro via its Effects on Coagulation and Inflammatory
Pathways
1
Jaehan Kim, 1Ahlam Abuawad, 1Vandhana M-Chari, Shaker A. Mousa1
1
Department of Biological Sciences, University at Albany, SUNY, Albany, NY; 2Pharmaceutical Research
Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Self-assembly of Green Tea Catechin Derivatives Nanoparticles for Oral Lycopene Delivery
Weikun Li, Melamangalam S Jayaraman, Dhruba Bharali, Shaker A. Mousa
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
Histone Binding and Ligand Recognition by the ATAD2b Bromodomain
1
Jonathan T. Lloyd, 1Jaime Gay, 2Brian E. Eckenroth, 2Sylvie Doublie, 1Karen C. Glass
1
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT;
2
Department of Microbiology and Molecular Genetics
University of Vermont, Burlington, VT
MicroRNA-21 and MicroRNA-15A Expression in Human Breast Cancer (MDA-MB-231) Cells Exposed to
Nanoparticulate Tetraiodothyroacetic Acid (Nanotetrac)
1
Shaker A. Mousa, 1Sudha Thangirala, 2Hung-Yun Lin, 1Heng-Yuan Tang, 3Gennadi V. Glinsky, 1, 4Paul J. Davis
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY; 2College of
Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 3Stanford University, Palo Alto,
CA; 4Albany Medical College, Albany NY
Actions of Nanoparticulate Tetraiodothyroacetic Acid (Nanotetrac) on Human Prostate Carcinoma Xenograft
Growth, Vascularity and Integrin Response to Radiation
1
Shaker A. Mousa, 1Thangirala Sudha, 1Murat Yalcin, 2John T. Leith, 3Aleck Hercbergs, 4Hung-Yun Lin,
1
Heng-Yuan Tang, 5Mary K. Luidens, 1,5Paul J. Davis
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY; 2Rhode
Island Nuclear Science Center, Narragansett, RI; 3Cleveland Clinic, Cleveland OH; 4Taipei Medical University,
Taipei, Taiwan; 5Albany Medical College, Albany, NY
20
POSTERS
Acting at a Plasma Membrane Receptor on Cancer Cells, Tetraiodothyroacetic acid (tetrac)
Nanoparticles are Pro-apoptotic, Anti-angiogenic, and Disrupt Expression of Multiple Cancer Cell
Survival Pathway Genes
1
Shaker A. Mousa, 1Dhruba J. Bharali, 1Murat Yalcin, 1Hung-Yun Lin, 1R. Meng, 1Heng-Yuan Tang, 1Faith B.
Davis, 1,3Paul J. Davis
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY;
2
Albany Medical College, Albany, NY
Bioequivalence of Chemoenzymatically Synthesized Bioengineered Heparin versus Porcine USP
Heparins
1
Shaker A. Mousa, 1Majde Takieddin, 1Nicole Vartigian, 2Jonathan S. Dordick, 2Jian Liu, 2Robert J. Linhardt
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY;
2
Rensselaer Polytechnic Institute, Troy, NY
Investigating Transdermal Diffusion of Vitamin D3 and 25-Hydroxyvitamin D3
Isaac Mall and F. Marcel Musteata
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY
Fragment-Based Prediction of Drug Distribution Across the Headgroup and Core Strata of a
Phospholipid Bilayer: Hexadecane-DiAcetyl Phosphatidyl Choline as Surrogate Phases
Senthil Natesan, Sandra Lynch, Rajesh Subramaniam, Iswarya Mathew, Zhanbin Wang, Stefan Balaz
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT
Thyroid Cancer Incidence Attributable to Overdiagnosis in the United States 1981-2011
1,2
Thomas J. O’Grady, 2,3Margaret A. Gates, 2,4Francis P. Boscoe
1
Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY;
2
School of Public Health; University at Albany, Rensselaer, NY; 3Bureau of Chronic Disease Evaluation and
Research, New York State Department of Health, Albany, NY; 4Bureau of Cancer Epidemiology, New York
State Department of Health, Menands, NY
Disparities in Papillary Thyroid Cancer Survival
1,2
Thomas J. O’Grady, 2A. Gregory DiRienzo, 2,3Francis P. Boscoe
1
Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY;
2
School of Public Health, Department of Epidemiology and Biostatistics University at Albany, Rensselaer, NY;
3
Bureau of Cancer Epidemiology, New York State Department of Health, Albany, NY
The Roots of Contemplative Traditions in Euro-America: Religious and Cultural Influences
in the Life of G.I. Gurdjieff
Michael Pittman
Department of Humanities and Communication, Albany College of Pharmacy and Health Sciences, Albany, NY
Synthesis of New Analog of Tetraidothyroacetic Acid (tetrac) as Novel Pro-angiogensis Molecule
1
Mehdi Rajabi, 1Thangirala Sudha, 1,2Noureldien H.E. Darwish, 1,3Paul J. Davis, 1Shaker A. Mousa
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY;
2
Faculty of Medicine, Mansoura University, Egypt; 3Albany Medical College, Albany, NY
21
POSTERS
Molecular Regulation of Host Inflammation during Influenza A Virus Infection
1
Bethany Reid, 1Rachel Visconti, 1Clare Williams, 1Rachel Wurth, 2Jonathan Harton , 1Eric J Yager
1
Albany College of Pharmacy & Health Sciences, Albany, NY; 2Center for Immunology and Microbial Disease,
Albany Medical College, Albany, NY
Downregulation of Bmi1 in Breast Cancer Stem Cells Suppresses Tumor Growth and Proliferation
1
Mathangi Srinivasan, 1Dhruba J. Bharali, 1Thangirala Sudha, 2Stewart Sell, 1Shaker A. Mousa
1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY
2
Wadsworth Center, New York State Department of Health, Albany, NY
Adherence Talk: Pharmacists’ Perspectives on the Challenges and Strategies of Patient-Centered
Communication
1
Amaal N. Yehia , 2Paul M. Denvir
1
Health and Human Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY; 2Department of
Humanities and Communication
Albany College of Pharmacy and Health Sciences, Albany, NY
22