Glutaminase Inhibitor CB839 Increases Radiation Sensitivity of Lung Tumor Cells and Human Lung Tumor Xenografts in Mice.

Medical students praised Dr. Alan Diekman for his teaching efforts during a recent breakfast with Dean Westfall.  Congratulations Dr. Diekman!

Samantha Kendrick, Ph.D.

Assistant Professor, Department of Biochemistry and Molecular Biochemistry and
Department of Pathology (secondary appointment)
UAMS College of Medicine

Research Interest Statement

Non-Hodgkin’s lymphoma has the ninth highest incidence rate in Arkansas, with diffuse large B-cell lymphoma (DLBCL) as the most commonly diagnosed subtype. Current treatment fails to achieve long-term disease-free survival in about 40 percent of DLBCL patients, either as upfront resistance to first-line therapy or following relapse after successful initial treatment. Our laboratory is dedicated to understanding the mechanisms behind aggressive forms of this malignancy and discovering new therapeutic strategies to improve patient outcome. In order to address this important area of cancer research, we integrate basic and translational science by utilizing ex vivo, cell line and tumor tissue-based models, paired with genomic and proteomic approaches. Ongoing projects include teasing out why certain oncogenes are susceptible to genomic instability, how DNA secondary structures may play a role in this process and can serve as novel targets for therapy, the impact of HIV infection on the development of lymphoma, and the differences between lymphoma that develops in children compared to adults.

Grants

UAMS Foundation Fund Board

Medical Research Endowment Award

Exploring DNA secondary structures as new therapeutic targets for aggressive lymphoma

1/1/2019 – 12/31/2019

$15,000*

 

Winthrop P. Rockefeller Cancer Institute Foundation Envoys

Seeds of Science Award

Identifying DNA sequence motifs critical for mutations in diffuse large B-cell lymphoma

2/15/2018 – 2/14/2019

$10,000*

* cancer-related annual direct costs

Dr. Kendrick’s UAMS Collaborators

Brendan Frett, Ph.D. (Pharmaceutical Sciences)

Stephanie Byrum, Ph.D. (Director of Bioinformatics Core, Arkansas Children’s Research Institute)

Timothy Chambers, Ph.D. (Biochemistry and Molecular Biology)

Ginell Post, M.D. (Pathology)

Dr. Kendrick’s External Collaborators

David Schatz, Ph.D. (Yale University; Howard Hughes Medical Institute)

Elizabeth Connick, M.D. (University of Arizona)

Amy Chadburn, M.D. (Cornell University)

Christian Stiedl, Ph.D. (University of British Columbia; British Columbia Cancer Agency)

Shankar Balasubramanian, Ph.D. (Cambridge University)

David Tannahill, Ph.D. (Cambridge University)

Opportunities for Collaboration

I welcome collaborations with basic and physician scientists, hematology oncologists, pathology fellows and residents, and bioinformaticians interested in joining forces to combat aggressive lymphoma and reduce the mortality of lymphoma patients.

You Might Not Know That

I am originally from the Great White North, and similar to my fellow Canadians, I enjoy maple syrup, hockey and bundling up next to the fire to read a good book.

Cancer-Related Publications

Kendrick S, Muranyi A, Gokhale V, Hurley LH, Rimsza LM. Simultaneous drug targeting of the promoter MYC G-quadruplex and BCL2 i-motif in diffuse large B-cell lymphoma slows tumor growth. J Med Chem 2017; 60:6587-97.

Kendrick S, Rimsza LM, Scott DW, et al. Aberrant cytoplasmic expression of MHCII confers worse progression free survival in diffuse large B-cell lymphoma. Virchows Arch 2017; 470:113-117.

Kendrick S, Tus K, Wright G, et al. Diffuse large B-cell lymphoma cell-of-origin classification using the Lymph2Cx assay in the context of BCL2 and MYC expression status. Leuk Lymphoma 2016; 57:717-20.

Li L, Pongtornpipat P, Tiutan T, Kendrick SL, et al. Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1. Leukemia 2015; 29:1702-12.

Alan Tackett, Ph.D., Professor of Biochemistry and Scharlu Family Endowed Chair in Cancer Research, was named as the Arkansas Biosciences Institute Established Investigator of the Year for his work on histone epigenetic mechanisms that regulate gene transcription and that are coupled to melanoma progression.  He is also the director of the Center for Translational Pediatric Research and the IDeA National Resource for Proteomics.  Congratulations Dr. Tackett!

Nov. 15, 2018 | A team of University of Arkansas for Medical Sciences (UAMS) research scientists recently was awarded a $1.8 million, five-year grant by the National Institute on Aging to investigate common pathways that contribute to the aging of various tissues.

Robert Shmookler Reis, D. Phil, professor in the UAMS College of Medicine’s Donald W. Reynolds Department of Geriatrics, and Srinivas Ayyadevara, associate professor in same department, are the co-principal investigators leading the study. Co-investigators are Steve Barger, Ph.D., professor in the Departments of Geriatrics and Neurobiology & Developmental Sciences, and Alan Tackett, professor in the Department of Biochemistry & Molecular Biology.

The goal of the research is to identify what different neurodegenerative diseases like Alzheimer’s disease have in common with other age-progressive diseases and conditions such as heart disease, muscle wasting, kidney disease, and type 2 diabetes.

Protein aggregation — clustering or clumping of protein molecules — has long been recognized as a hallmark of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

“We were the first ones to show that protein aggregation happens not just in the brain, but also in the heart, skeletal muscle and kidney with age and age-associated diseases,” Ayyadevara said.  Reis added, “The misfolding of proteins, which contributes to protein aggregation, is promoted by stress and inflammation, accumulating with age.”

Reis said the team has looked at protein aggregation for nearly a decade, funded by grants from the U.S. Department of Veteran Affairs.  For the last two years, it has also been supported as part of a multi-investigator National Institutes of Health (NIH) grant led by Sue Griffin, Ph.D., professor and vice chair of research at the UAMS Donald W. Reynolds Institute on Aging.  Peter Crooks, Ph.D., D.Sc., chair and professor of the Department of Pharmaceutical Sciences in the UAMS College of Pharmacy, developed novel derivatives of anti-inflammatory drugs.

As part of the NIH grant, Crooks, Reis, Ayyadevara, and graduate student Samuel Kakraba tested these drugs for their ability to inhibit protein aggregation and to extend life. One drug, PNR502, was the main subject of a recently awarded patent covering several bioactive compounds.

“It not only inhibits further protein aggregation but even appears to reverse it,” Ayyadevara said. “Working with Dr. Barger, we will examine whether it can preserve youthful functions in the hearts and brains of normal mice, and in a mouse model of Alzheimer’s.”

“We have shown that protein aggregation accompanies aging of all tissues, and probably contributes causally to most or all age-associated diseases,” said Reis. “This fundamental molecular process may underlie most of the deterioration that defines aging. It’s a Pandora’s box that holds all the things that go wrong as we get older, so it offers an unprecedented opportunity to finally understand how and why so many disparate factors contribute to aging.”

Oleg Karaduta from Boris Zybaylov’s lab was invited to give an oral talk at the Second Global Summit and EXPO on Proteomics in Dallas, TX. His presentation highlighted the basics of metaproteomics data processing pipe-line, its application to the study of function of gut microbiome in chronic kidney disease and current results of their research.

Researchers at the University of Arkansas for Medical Sciences (UAMS) have received a $604,208 grant to study how an abnormal protein found in ovarian cancer and some brain tumors helps tumors grow.

The National Institutes of Health (NIH) awarded the three-year grant to Karen Abbott, Ph.D., assistant professor in the UAMS College of Medicine’s Department of Biochemistry and Molecular Biology, and Analiz Rodriguez, M.D., Ph.D., assistant professor in the UAMS College of Medicine’s
Department of Neurosurgery. Abbott is principal investigator for the grant, and Rodriguez is co-investigator.

The pair are researching glycosylation changes, which are found in both ovarian cancer and glioblastoma, an aggressive brain tumor. Glycosylation is the enzymatic process that attaches glycans (a series of carbohydrates, including the sugars) to proteins, or other organic molecules.

In her previous research, Abbott developed an antibody that targets glycosylation on proteins covering the surface of ovarian cancer cells. The new project involves adapting that protein into a new type of therapy for the disease and examining if it also could serve as an effective therapy for glioblastoma, which shares the same type of glycosylation.

“This research can help us understand the proteins that carry this glycosylation change and how this change promotes signals to keep cancer cells alive. Studying those pathways may lead to new methods to kill the cancer cells but leave the normal ones alone,” said Rodriguez, a neurosurgeon
and researcher.

“With this grant, we will be developing a new type of therapeutic by modifying the current antibody to allow destruction of the cancer cells,” Abbott said.

In their work, Rodriguez’s lab, which focuses on glioblastoma, will provide tumor samples from patients to test this novel therapy.

Rodriguez and Abbott, whose labs are next door to each other, decided to team up after learning of each other’s research and discovering it intersected.

“We decided it would be a good idea to join forces and work on something together,” Rodriguez said.

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Congratulations to the Wahls lab for their recent publication in Epigenetics & Chromatin.

Chromatin-mediated regulators of meiotic recombination revealed by proteomics of a recombination hotspot