Congratulations to Lauren Davis who successfully defended her dissertation entitled “Histone Posttranslational Modifications as Diagnostic Markers for Melanoma” on February 20th.  Lauren is a student in Alan Tackett’s lab.

Oleg Karaduta was selected to receive a Young Investigator Educational Grant to study clinical application of mass spectrometry during the MSACL 11^th Annual Conference.

Curriculum includes short courses, practical training sessions and a variety of workshops.  Congratulations Dr. Karaduta!

Feb. 5, 2019 | Researchers at the UAMS Winthrop P. Rockefeller Cancer Institute received a funding boost thanks to the efforts of two volunteer groups.

One small grant award of $50,000 and three pilot awards of $15,000 each were presented to UAMS cancer researchers at a reception and research poster showcase hosted by the Envoys volunteer advocacy group Jan. 31.

The small grant award was funded by proceeds from the 17^th annual Village Walk for Cancer Research, held Sept. 29, 2018 in Hot Springs Village. Organized by volunteers, the walk unites the community, which is located one hour southwest of Little Rock, in support of cancer research.

“Knowing the money we raise is used to advance cancer research right here in Arkansas is very satisfying for those of us who organize the walk and participate in it,” said Melanie Pederson, event chair. Donna Aylward serves as co-chair.

Since 2002, the Village Walk for Cancer Research has raised about $500,000 for research programs at the UAMS Cancer Institute. The 2019 walk is scheduled for Sept. 28 at Balboa Pavilion in Hot Springs Village.

A team of two researchers received the small grant award for their work addressing drug resistance to aggressive lymphoma.

Brendan Frett, Ph.D., assistant professor in the Department of Pharmaceutical Sciences in the UAMS College of Pharmacy, and Samantha Kendrick, Ph.D., assistant professor of Department of Biochemistry and Molecular Biology in the UAMS College of Medicine, are collaborators on the project. They are exploring using a proteolysis targeting chimera molecule along with targeted therapies to break down the cancer-promoting protein Nek2

found in aggressive lymphoma. This dual treatment approach has the potential to reduce drug resistance and lead to better patient outcomes.

Three $15,000 pilot awards were presented to researchers for their work in a variety of areas. Funding for the awards was made possible by RockStar Lounge, an annual fundraising event hosted by the Envoys.

This year’s RockStar Lounge is set for April 5 at Cajun’s Wharf in Little Rock and will feature a performance by Memphis-based band Doctor Zarr’s Amazing Funk Monster. One-hundred percent of the net proceeds from RockStar Lounge is used to fund cancer research projects at UAMS.

“We are always excited and pleased to present grants to our very worthy scientists for their innovative projects,” said Jenny Long, Envoys president.

Recipients of the pilot awards were:

• Alicia Byrd, Ph.D., and Stephanie Byrum, Ph.D., assistant professors in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine

Byrd and Byrum’s project aims to identify new targets for cancer therapy by investigating the regulation of the DNA damage response pathway in cancerous and normal cells.

• Robert Eoff, Ph.D., associate professor in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine

Eoff’s project attempts to determine if a regulatory pathway normally associated with immune suppression in brain tumors also plays a role in resistance to the anti-cancer drug Temodar. Results of this study could increase understanding of how the elements involved in treatment resistance are regulated in malignant brain tumors.

• Zhiqiang Qin, M.D., Ph.D., associate professor in the Department of Pathology in the UAMS College of Medicine

The subtype of lung cancer known as non-small cell lung cancer (NSCLC) is a leading cause of cancer death in Arkansas. Qin’s project examines the use of the gene EIF4G1 as a therapeutic target for NSCLC and could provide the framework for the development of a clinical trial evaluating EIF4G1-targeted therapy.

 

 

 

Congratulations to Dr. Isabelle Racine-Miousse who received a pilot grant from the Barton Foundation for her studies of methionine and autophagy in metastatic melanoma.

Scientific discovery could be accelerated with more open access to genomic data, says an article in the latest journal Science by a group of research leaders from across the globe that includes David W. Ussery, Ph.D., at the University of Arkansas for Medical Sciences (UAMS).

“We argue that the publicly available data should be treated as open data, a shared resource with unrestricted use for analysis, interpretation and publication,” the article states in the journal’s Policy Forum titled, “Toward unrestricted use of public genomic data.”

The article, with 51 authors, challenges long-standing customs and guidelines that have allowed the producers of genomics data to keep it for analysis and publication before outside researchers can study it.

As a specialist in bacterial genomics, Ussery, a professor in the UAMS College of Medicine Department of Biomedical Informatics, said a better understanding of genome sequences will help scientists more easily determine where outbreaks originate and how they can be treated.

“In my field, it is critical to have unrestricted access to this kind of genomic data,” said Ussery, a member of the international Genomics Standards Consortium. “Some of our biggest scientific advances are likely to come from genomics research, and we need to remove barriers that could delay discoveries.”

The article calls for revising the landmark 2003 Fort Lauderdale Agreement, which is a public declaration by scientists supporting free and unrestricted use of genome sequencing data. The agreement, the authors say, is “self-contradictory” because it also recommends a hands-off approach to publicly available data so that those who produced the data have a chance to analyze and publish it.

A key factor in the article’s push is the growing wave of raw data from faster, inexpensive third-generation genome sequencing devices, said Ussery, who holds the Helen Adams & Arkansas Research Alliance Endowed Chair in Bioinformatics.

“By 2025, the amount of data from third-generation sequencing will dwarf other big data generators like Youtube and Twitter,” Ussery said. “Youtube is expected to reach 2 exabytes, but third-generation sequencing will produce about 20 zettabytes of data.” A zettabyte is 1,000 times larger than an exabyte.

In a recent presentation, Ussery cited the 20 zettabyte projection for genetic sequencing data, noting that the estimated cost to store that much data is $2 trillion.

In fact, with the advent of large global data analysis studies, the article says, the amount of publicly available data is at the scale of yottabytes (1,000 times larger than a zettabyte).

Scientific analysis of so much data requires costly computing resources and advanced analytical capabilities, and some scientists who produce genomic data don’t have those advanced capabilities. In those cases, outside researchers should be allowed free access to the data without restriction.

“For example,” the article states, “the outsider team may have better analytical capabilities and/or overarching protocols for analyzing more comprehensive sets of data, pre- or post-publication. Also, sequence datasets can be interrogated by means of numerous value-added platforms and tools from multiple groups.”

The article cites three guiding principles for their recommendations:

• Public genomics data that have ethics approval for release should be open data – available for unrestricted use, together with associated metadata – with the exception of sensitive human data to which additional ethics restrictions may apply
• Science advances through open competition with clear-cut, transparent rules, not through posing restrictions and limitations
• Credit should be given appropriately to resource producers (those who produce the data) and should be transparent.

“These recommendations should not impede protection of sensitive human data,” the article states. “We acknowledge that for existing sensitive human data, some restrictions may be appropriate.”

The article is available here: http://science.sciencemag.org/content/363/6425/350.

 

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.