Congratulations to Aaron Storey and his co-authors on their publication featured on the August 2020 cover of Molecular Omics. The project was a collaboration between multiple labs and the proteomics and bioinformatics core facilities lead by Stephanie Byrum.
News
Alan Tackett receives $10.6 Million Grant to Expand National Proteomics Resource at UAMS
A $10.6 million grant from the National Institutes of Health (NIH) will allow the University of Arkansas for Medical Sciences (UAMS) to greatly expand its proteomics resource. This grant will establish the IDeA National Resource for Quantitative Proteomics as the first NIH National Resource in Arkansas, which will serve biomedical researchers across the nation.
Proteomics is the large-scale study of proteins that can lead to the development of new therapies and screening approaches for many diseases, including cancer.
The five-year grant was awarded to Alan Tackett, Ph.D., professor in the Department of Biochemistry and Molecular Biology and associate director for basic science at the UAMS Winthrop P. Rockefeller Cancer Institute. Tackett serves as an administrative director of this new national resource.
Other key contributors at UAMS are Rick Edmondson, Ph.D.; Samuel Mackintosh, Ph.D.; and Stephanie Byrum, Ph.D.; as well as Michael Kinter, Ph.D., at the Oklahoma Medical Research Foundation who serves as a co-administrative director.
The national resource was initially created through the Arkansas INBRE (IDeA Network of Biomedical Research Excellence) — an NIH program that promotes biomedical research for undergraduate students and faculty. Lawrence Cornett, Ph.D., professor in the UAMS College of Medicine Department of Physiology and Biophysics, serves as principal investigator and director of Arkansas INBRE.
“With this new funding, we will transition our proteomics resource to an NIH National Resource and expand our ability to provide highly advanced research support to scientists in underfunded areas throughout the United States,” said Tackett, who holds the Scharlau Family Endowed Chair for Cancer Research at UAMS.
Certain regions of the United States, designated as the IDeA Network, have historically received low levels of research funding from NIH. Scientists in these regions face challenges for accessing state-of-the-art proteomics resources.
The IDeA National Resource for Quantitative Proteomics at UAMS was established to address these gaps in services.
“Due to a lack of federal funding, it is often difficult for scientists in the IDeA Network to access the advanced instruments and trained personnel needed to analyze and interpret their research data. With this new funding, we will now be able to serve a diverse group of IDeA investigators for their research, which ranges from studies on model organisms to diseases such as cancer,” said Tackett, professor of biochemistry and molecular biology in the UAMS College of Medicine.
The expanded national resource will support researchers by providing highly advanced data analysis, outreach opportunities and education to scientists across the nation.
“Our goal is to increase the ability for scientists in the 23 IDeA states and Puerto Rico, as well as other NIH-supported investigators across the nation, to perform innovative research by providing unmatched access to advanced quantitative proteomics platforms and staff skilled in interpreting and analyzing complex biological data,” Tackett said.
The educational opportunities offered by the national resource include workshops that are designed to help faculty and student researchers across the nation better utilize proteomics in their research.
This federal grant will bolster the Cancer Institute’s ongoing efforts to receive National Cancer Institute Designation. To achieve designation, cancer centers undergo a highly competitive assessment process that demonstrates an outstanding depth and breadth of research in three areas: basic laboratory, patient/clinical and population-based. The designation brings with it many benefits, including expanded access to federal funding for researchers and improved access to clinical trials for patients.
Cancer Institute Member Spotlight
Alan Diekman, Ph.D.
Professor
Department of Biochemistry and Molecular Biology
Department of Urology
UAMS College of Medicine
Research Interest Statement
Research in the Diekman laboratory focuses on galectin-3, a carbohydrate-binding protein, in cancer and normal male reproductive function. Galectin-3 is implicated in the progression of multiple cancers, including prostate and breast cancer. Previously, we investigated the interactions of galectin-3 with prostate specific antigen (PSA), which is mainly known as a screening marker for prostate cancer. PSA is a serine protease that is secreted into semen where it functions as a proteolytic enzyme. PSA function during local and metastatic prostate cancer has also been proposed. We were the first to demonstrate that galectin-3 is a proteolytic substrate for PSA and investigated the function regulation of galectin-3 by PSA. We developed a novel strategy to purify PSA for these studies. Significantly, polymorphisms (SNP) in the coding region of the human galectin-3 gene create amino acid polymorphisms in the galectin-3 protein, and genotype analysis indicated that these SNPs are associated with increased odds of prostate cancer. We currently are investigating the impact of these amino acid polymorphisms on the molecular function of galectin-3. We anticipate that elucidation of the functional aspects of galectin-3 phenotypic variation relevant to disease etiology and pathology will contribute to development of individualized, precision medicine strategies to improve cancer prevention and treatment.
Dr. Diekman’s Cancer-related Grants
UAMS Executive Breast Committee: AWD00051704
Alan Diekman: PI
Title “Galectin-3 Genetic and Phenotypic Polymorphism in Breast Cancer”
09/1/2016 – 08/31/2020
$75,000*
*cancer-related direct cost
Dr. Diekman’s UAMS Collaborators
Alicia Byrd, Ph.D., Department of Biochemistry and Molecular Biology, College of Medicine
Joseph Su, Ph.D., M.P.H., Department of Epidemiology, College of Public Health
Opportunities for Collaboration
I have expertise in biochemistry, reproductive biology and glycobiology and am always interested in collaborating with colleagues. My research is focused on the role of carbohydrate-binding proteins in prostate cancer, but my interests extend to other cancers, including breast and colorectal cancer.
You May Not Know That …
I am the proud owner of a 1923 arts and crafts airplane bungalow in Hillcrest, but something always needs to be fixed. My hobbies include physical fitness, science fiction and annoying my children with dad jokes.
Recent Cancer-related Publications
Saraswati, S., Block, A.S., Davidson, M.K., Rank, R.G., Mahadevan, M., Diekman A.B. (2011) Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal plasma. The Prostate 71:197-208, DOI: 10.1002/pros.21236. PMCID: PMC3606048.
Kovak M.R., Saraswati S., Goddard, S., Diekman A.B. (2013) Proteomic identification of galectin-3 binding ligands and characterization of galectin-3 proteolytic cleavage in human prostasomes. Andrology 1:682-691, PMCID: PMC4180284.
Bailey, L.A., Jamshidi-Parsian A., Patel T., Koonce N.A., Diekman A.B., Cifarelli .P., Marples B., Griffin R.J.: (2015) Combined temozolomide and ionizing radiation induces galectin-1 and galectin-3 expression in a model of human glioma. Tumor Microenvironment and Therapy 2:19-31.
Dr. Tackett appointed to NIH study section
Dr. Alan Tackett, Professor of Biochemistry and Molecular Biology, has been invited to serve as a standing member of the NIH Mechanisms of Cancer Therapeutics-1 (MCT1) Study Section, one of the major review boards for evaluation of cancer research by the Center for Scientific Review. The four-year appointment recognizes Dr. Tackett, who also serves as the Scharlau Family Endowed Chair in Cancer Research at UAMS, as a leader in this field. Congratulations to Dr. Tackett.
July publications
Neonatal Diet Impacts Circulatory miRNA Profile in a Porcine Model.
Carr LE, Bowlin AK, Elolimy AA, Byrum SD, Washam CL, Randolph CE, MacLeod SL, Yeruva L.
Front Immunol. 2020
Novel advances in biotransformation and bioactivation research-2019 year in review.
Khojasteh SC, Driscoll JP, Jackson KD, Miller GP, Mitra K, Rietjens IMCM, Zhang D.
Drug Metab Rev. 2020
Dr. Miller Appointed to NIH Study Section
Congratulations to Dr. Grover Miller, Professor of Biochemistry and Molecular Biology, on his appointment to the Xenobiotic and Nutrient Disposition and Action (XNDA) Study Section in the National Institutes of Health’s Center for Scientific Review. Dr. Miller will serve a four-year term on the panel, whose members are selected for their excellence and achievement in their scientific discipline. At UAMS, Dr. Miller and his team develop and apply new and powerful strategies to better assess drug liabilities that cause significant adverse drug events including cardio- and hepato-toxicity.
Brian Koss student highlight
Brian is a Ph.D. student starting his fifth year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Alan Tackett.
He has a B.A. in Biochemistry and Molecular Biology from Hendrix College.
Research Interest Statement
My doctoral work focuses on the dynamic interplay between the epigenetic and metabolic pathways used by T cells to sense and respond to environmental pressures. Specifically, I focused on the loss of the histone methyltransferase EZH2 (H3K27me3) in CD8+ T cells, which occurs during solid tumor infiltration and renders T cells dysfunctional. My work revealed loss of H3K27me3 leads to mitochondrial dysfunction and metabolic exhaustion, through a Cdkn2a.ARF-mediated, p53-independent mechanism. Reprogramming T cells to express a gain-of-function EZH2 mutant enhanced inhibition of tumor growth in a model of adoptive T cell therapy. My data suggest manipulation of EZH2 in T cells represents a potential strategy to protect tumor-specific T cells, which is currently unaccounted for in the clinical development of EZH2 inhibitors.
Career Goals
Once I am finished with my PhD, I plan to continue my current work and pursue early independence opportunities.
Experiment or Technique You Would Most Like to Do
This changes from time to time. However, I currently enjoy using proteomic approaches to interrogate protein turnover rates at a proteome level. I believe this approach will give us novel insights into how a cell prepares its proteome for rapid adaptation to environmental conditions.
Fun fact
My wife, Cary, and I have two boys, Bennett (5 years) and Parker (3 years).
Publications
- Koss, B.; Shields, B. D; Taylor, E. M.; Storey, A. J.; Byrum, S. D.; et. al. Epigenetic control of Cdkn2a.Arf protects tumor-infiltrating lymphocytes from metabolic-exhaustion. Cancer Research, (accepted).
- Trentzsch, M.; Nyamugenda, E.; Miles, T. K.; Griffin, H.; Russell, S.; Koss, B.; Cooney, K. A.; Phelan, K. D.; Tackett A. J., Iyer, S.; Boysen, G.; Baldini, G. Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum. Cell Death Discovery 6:8 (2020).
- Taylor, E.; Koss, B.; Davis L. E.; Tackett, A. J. Histone Modifications as Biomarkers for Immunotherapy. Methods in Molecular Biology 2055:213-228 (2019).
- Chiang, T.; Koss, B.; Su, L. J.; Washam, C. L.; Byrum, S. D.; Storey, A.; Tackett, A. J. Effect of sulforaphane and 5-aza-2’-deoxycytidine on melanoma cell growth. Medicines 6, 71 (2019).
- Lee, T.; Christov, P. P.; Shaw, S.; Tarr, J. C.; Zhao, B.; Veerasamy, N.; Jeon, K. O.; Mills, J. J.; Bian, Z.; Sensintaffar, J. L.; al. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. Journal of medicinal chemistry 62, 3971–3988 (2019).
- Shields, B. D.; Koss, B.; Taylor, E. M.; Storey, A. J.; West, K. L.; Byrum, S. D.; Mackintosh, S. G.; Edmondson, R.; Mahmoud, F.; Shalin, S. C.; Tackett, A. J. Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma. Cancer Research 79, 1113–1123 (2019).
- Ren, Z.; Ahn, J. H.; Liu, H.; Tsai, Y.-H.; Bhanu, N. V; Koss, B.; Allison, D. F.; Ma, A.; Storey, A. J.; Wang, P. PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation. Blood blood-2019000578 (2019).
- Shields, B. D.; Mahmoud, F.; Taylor, E. M.; Byrum, S. D.; Sengupta, D.; Koss, B.; Baldini, G.; Ransom, S.; Cline, K.; Mackintosh, S. G. Indicators of responsiveness to immune checkpoint inhibitors. Scientific Reports 7, 807 (2017).
- Lee, T.; Bian, Z.; Zhao, B.; Hogdal, L. J.; Sensintaffar, J. L.; Goodwin, C. M.; Belmar, J.; Shaw, S.; Tarr, J. C.; Veerasamy, N.; Matulis, S. M.; Koss, B.; Fischer, M. A.; Arnold, A. L.; Camper, D. V.; Browning, C. F.; Rossanese, O. W.; Budhraja, A.; Opferman, J.; Boise, L. H.; Savona, M. R.; Letai, A.; Olejniczak, E. T.; Fesik, S. W. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Letters 591, 240–251 (2017).
- Koss, B.; Ryan, J.; Budhraja, A.; Szarama, K.; Yang, X.; Bathina, M.; Cardone, M. H.; Nikolovska-Coleska, Z.; Letai, A.; Opferman, J. T. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget 7, (2016).
- Haverkamp, J. M.; Smith, A. M.; Weinlich, R.; Dillon, C. P.; Qualls, J. E.; Neale, G.; Koss, B.; Kim, Y.; Bronte, V.; Herold, M. J.; Green, D. R.; Opferman, J. T.; Murray, P. J. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity 41, 947–959 (2014).
- Koss, B.; Morrison, J.; Perciavalle, R. M.; Singh, H.; Rehg, J. E.; Williams, R. T.; Opferman, J. T. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 122, 1587–1598 (2013).
- Tripathi, P.; Koss, B.; Opferman, J. T.; Hildeman, D. A. Mcl-1 antagonizes Bax/Bak to promote effector CD4(+) and CD8(+) T-cell responses. Cell death and differentiation 20, 998–1007 (2013).
- Wang, X.; Bathina, M.; Lynch, J.; Koss, B.; Calabrese, C.; Frase, S.; Schuetz, J. D.; Rehg, J. E.; Opferman, J. T. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes and Development 27, 1351–1364 (2013).
- Cohen, N. A.; Stewart, M. L.; Gavathiotis, E.; Tepper, J. L.; Bruekner, S. R.; Koss, B.; Opferman, J. T.; Walensky, L. D. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chemistry and Biology 19, 1175–1186 (2012).
- Perciavalle, R. M.; Stewart, D. P.; Koss, B.; Lynch, J.; Milasta, S.; Bathina, M.; Temirov, J.; Cleland, M. M.; Pelletier, S.; Schuetz, J. D.; Youle, R. J.; Green, D. R.; Opferman, J. T. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature Cell Biology 14, 575–583 (2012).
- Stewart, D. P.; Koss, B.; Bathina, M.; Perciavalle, R. M.; Bisanz, K.; Opferman, J. T. Ubiquitin-independent degradation of antiapoptotic MCL-1. Molecular and cellular biology 30, 3099–3110 (2010).
Complete List of Published Work:
https://www.ncbi.nlm.nih.gov/myncbi/1pihpxbtPQJQh/bibliography/public/
Grants
- 2019-present NIH/NCI F31 predoctoral fellowship. Epigenetic regulation of metabolic stress pathways in melanoma infiltrating lymphocytes (F31CA232464). 7th percentile. $124,851
- 2019 Department of Defense Horizon Award. Epigenetic regulation of metabolic stress pathways in melanoma infiltrating lymphocytes. Recommended for funding as alternate.
- 2017-2018 Systems Pharmacology and Toxicology Graduate Fellowship, a T32 program; University of Arkansas for Medical Sciences.
Awards
- 2020 Sanofi Scholar-in-Training Award. American Association for Cancer Research (AACR), San Diego, CA
- 2020 Keystone Symposia Scholarship. Emerging Cellular Therapies: Cancer and Beyond. Banff, AB Canada
- 2019 Cancer Institute Member Spotlight. University of Arkansas for Medical Sciences, Little Rock AR.
- 2019 Graduate School Outstanding Achievement Award. University of Arkansas for Medical Sciences, Little Rock AR.
- 2018 Immuno-Oncology Innovation Award, Miltenyi Biotec. Fully paid travel to AACR 2018 and $2500 for research.
Alumnus Highlight: Michael Guderyon
Michael Guderyon graduated from UAMS in may 2015 with an M.S. in Biochemistry and Molecular Biology. His advisor was Dr. Kevin Raney. After graduating, Mike went to UT Health San Antonio where he received a Ph.D. in Integrated Biomedical Sciences/ Biology of Aging Track. Mike is currently a Process Development Scientist I at SanBio. In addition, he’s in the Airforce Reserves and is an entrepreneur.
Description of Current Job
Combines extensive knowledge of biotechnology and bio-manufacturing to manufacture mesenchymal stem cell products and monitor existing processes and products for quality and efficiency. Problem-solves and conceptualizes solutions for producing large scale stem cell products and standardizes protocols.
- Works hand and hand with Quality Control to develop and qualify potency assays for cell-based products
- Design and execute experiments in support of process optimization of cell-based products and process improvement
- Leads statistical analyses of completed projects in collaboration with assay development and manufacturing teams
- Develops and implements processes to scale up manufacturing and automation of cell-based products
- Draft and author study protocols, feasibility, comparability, and qualification reports as source documents for regulatory filing support
Important Aspect of the Biochemistry and Molecular Biology Program
I was surrounded by excellent mentors at all levels which prepared me for the road ahead.
Something Notable about Time as a Graduate Student
Once during my studies, I was purifying a protein for future use and while formulating the final protein product, I accidentally threw away the entire protein. I am sure my colleagues and mentors sensed my embarrassment and were very supportive moving forward. I distinctly remember my mentor cracking a smile and saying, “always secure the ‘gold’ first”.
Fun Fact
I plan to earn an MBA in the future.
On the cover
Congratulations to postdoctoral fellow Maroof Zafar and his co-authors, Lindsey Hazeslip, Zain Chauhan, and Alicia Byrd. Cover art by Lindsey Hazeslip for their recent article on regulation of expression by non-canonical G-quadruplexes was selected for the cover of the July 2020 issue of Biochemistry.
June publications
Wongsurawat T, Jenjaroenpun P, De Loose A, Alkam D, Ussery DW, Nookaew I, Leung YK, Ho SM, Day JD, Rodriguez A.
Acta Neuropathol Commun. 2020
The Expression of Human DNA Helicase B Is Affected by G-Quadruplexes in the Promoter.
Zafar MK, Hazeslip L, Chauhan MZ, Byrd AK.
Biochemistry. 2020