Congratulations to Kanishka Manna, a graduate student in the lab of Stephanie Byrum, Ph.D., who won second place in the Bioinformatics Division at the SE IDeA meeting in Columbia, SC. His poster title was, “A novel proteogenomics workflow for proteoforms detection.”
I just started my sixth year in Biochemistry and Molecular Biology Ph.D. program and will graduate in October.
China Pharmaceutical University, B.S. in Pharmacy (Basic Pharmacy).
I have two research interests: 1) Discovery and optimization of novel inhibitors of clinically relevant targets 2) PROTAC and its applications. I have been working on multiple research projects within these research scopes.
I’m currently working on my dissertation thesis based on one of the projects, titled: Identification of Imidazo[1,2 a]pyridine pyridine derivatives as FLT3 kinase inhibitors for potential treatments of acute myeloid leukemia.
Acute myeloid leukemia (AML) is a hematologic cancer characterized by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML, found in approximately 30% of newly diagnosed cases, most commonly consisting of internal tandem duplication (ITD) mutations in the juxtamembrane region. Recently, several FLT3 inhibitors have demonstrated clinical activity and three are currently approved – midostaurin, quizartinib, and gilteritinib. However, their clinical efficacies are limited in part due to the emergence of secondary clinical resistance, caused by multiple mechanism including on-target FLT3 secondary mutations – FLT3-ITD/D835Y and FLT3-ITD/F691L being the most common, as well as the off-target activation of alternative pathways including the BCR-ABL pathway. Therefore, in order to overcome drug resistance and further improve outcomes, new compounds targeting FLT3-ITD with secondary mutants are urgently needed. In my works, three compounds were identified with potent anti-leukemic effects, and may be further developed for treatment of AML.
Throughout my Ph.D. periods, I got to know that research is never a solitary work. It requires frequent communication and close collaboration to get the work done.
I will seek postdoc training after my Ph.D. I have already accepted the postdoc offer at Dana-Farber Cancer Institute, Harvard Medical School, working with Dr. Jun Qi. My vision for my future career is to take on the academic path and be an independent principal investigator after the postdoc training.
Experiment or technique you would most like to do (could be something you enjoy doing or something you have never done but would like to get the opportunity to do)
I like the design and synthesis of new compounds because there is a sense of satisfaction in creating something new.
I like hiking and exploring nature.
Doctor of Philosophy students who passed their candidacy exams in the last year received their white coats at the Graduate School Research Induction Ceremony. Students from the Biochemistry and Molecular Biology Track who received their white coats were Reham Sewilam, mentored by Robert Eoff, Ph.D., Mason McCrury, mentored by Samantha Kendrick, Ph.D., and Randall Rainwater, mentored by Marie Burdine, Ph.D. Congratulations to all!
Cutting-Edge Technologies Driving Quantitative Mass Spectrometry.
Avaritt NL, Byrum SD.
J Vis Exp. 2023
Bioactivation and reactivity research advances – 2022 year in review.
Wang S, Argikar UA, Cheruzel L, Cho S, Crouch RD, Dhaware D, Heck CJS, Johnson KM, Kalgutkar AS, King L, Liu J, Ma B, Maw H, Miller GP, Seneviratne HK, Takahashi RH, Wei C, Khojasteh SC.
Drug Metab Rev. 2023
Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.
Chowdhury S, Kennedy JJ, Ivey RG, Murillo OD, Hosseini N, Song X, Petralia F, Calinawan A, Savage SR, Berry AB, Reva B, Ozbek U, Krek A, Ma W, da Veiga Leprevost F, Ji J, Yoo S, Lin C, Voytovich UJ, Huang Y, Lee SH, Bergan L, Lorentzen TD, Mesri M, Rodriguez H, Hoofnagle AN, Herbert ZT, Nesvizhskii AI, Zhang B, Whiteaker JR, Fenyo D, McKerrow W, Wang J, Schürer SC, Stathias V, Chen XS, Barcellos-Hoff MH, Starr TK, Winterhoff BJ, Nelson AC, Mok SC, Kaufmann SH, Drescher C, Cieslik M, Wang P, Birrer MJ, Paulovich AG.
Cell. 2023
Exosomal MicroRNA and Protein Profiles of Hepatitis B Virus-Related Hepatocellular Carcinoma Cells.
Todorova VK, Byrum SD, Mackintosh SG, Jamshidi-Parsian A, Gies AJ, Washam CL, Jenkins SV, Spiva T, Bowman E, Reyna NS.
Int. J. Mol. Sci. 2023
By Marty Trieschmann
Aug. 3, 2023 | The Birrer Laboratory at the University of Arkansas for Medical Sciences (UAMS) Winthrop P. Rockefeller Cancer Institute helped discover a proteogenomic signature in ovarian cancer that may improve the way the disease is treated around the world.
The discovery, which identifies a 64-protein-gene signature that can predict primary treatment resistance in patients with high grade ovarian cancer, was published Aug. 3 in the journal Cell.
Michael Birrer, M.D., Ph.D., director of the UAMS Winthrop P. Rockefeller Cancer Institute and UAMS vice chancellor, is a senior author on the Cell publication. Birrer, who was the co-principal investigator of the U01 grant from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, has a laboratory dedicated to the translation of the genomics of ovarian cancer into better treatment of the disease.
Amanda Paulovich, M.D., Ph.D., physician-scientist at Fred Hutchinson Cancer Center and Birrer’s co-author on the study, praised the UAMS team for its work.
“Mike’s decades of experience treating ovarian cancer patients was crucial to ensuring that our project goals and design were crafted to meet the needs of patients with the most devastating form of this disease — platinum refractory ovarian cancers.”
The Birrer Lab helped design, implement, analyze and interpret the results of the study and was critical in assuring the project had sufficient clinically annotated patient specimens for the state of the art proteomic/genomic analysis. His team characterized proteins and genetic markers in 242 high-grade serous ovarian cancers that responded or did not respond to treatment. The tumor samples were collected from patients before they began treatment.
The overall prognosis for women with high grade ovarian cancer is challenging, although the median survival rate has improved to five years. Unfortunately, patients with refractory tumors, those that do not respond to initial therapy, remains unchanged. These patients waste precious time going through initial treatments that do not work.
“Right now, we can’t identify these ovarian cancer patients up front. We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials,” said Birrer. “This study is a huge step forward in that.
“For the first time, we will know if a patient is unlikely to get better with standard treatment and make better recommendations for them to immediately explore other options like new therapeutics in clinical trials.”Further, the study identifies five subgroups of refractory tumors by specific activated pathways, some of which may be targetable.
The study was led by Paulovich, Birrer and Pei Wang, Ph.D., professor of Genetics and Genomic Sciences at the Icahn School of Medicine in Mount Sinai, NY.
A former Harvard Medical School professor, Birrer joined UAMS in 2019 after directing the O’Neal Comprehensive Cancer Center at the University of Alabama in Birmingham. A New Jersey native, he completed his medical degree and doctor of philosophy degree in 1982 in the Medical Scientist Training Program at the Albert Einstein College of Medicine in New York. He served his internship and residency at Massachusetts General Hospital, where he realized cancer treatment and research were improving by leaps and bounds. Inspired, Birrer entered the Medical Oncology Fellowship Program at the National Cancer Institute in Bethesda, Maryland. He was appointed professor of medicine at the Harvard School of Medicine and was director of Gynecologic Medical Oncology at Massachusetts General Hospital and the Gynecologic Oncology Research Program at the Dana-Farber/Harvard Cancer Center.
Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.
Ketkar A, Sewilam RS, McCrury MJ, Hall JS, Bell A, Paxton BC, Tripathi S, Gunderson JEC, Eoff RL.
RSC Chem Biol.
Musashi exerts control of gonadotrope target mRNA translation during the mouse estrous cycle.
Moreira ARS, Lim J, Urbaniak A, Banik J, Bronson K, Lagasse A, Hardy L, Haney A, Allensworth M, Miles TK, Gies A, Byrum SD, Wilczynska A, Boehm U, Kharas M, Lengner C, MacNicol MC, Childs GV, MacNicol AM, Odle AK.
Endocrinology.
UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair.
Lee SO, Kelliher JL, Song W, Tengler K, Sarkar A, Dray E, Leung JWC.
J Biol Chem.
By Nathan Tidwell
Students from 41 colleges and universities across the nation recently attended the 10th annual Arkansas Undergraduate Summer Research Symposium at the University of Arkansas for Medical Sciences (UAMS).
The symposium celebrated achievements by undergraduates pursuing research in a wide range of biomedical-related topics. The UAMS Department of Biochemistry and Molecular Biology organized and sponsored the event with support from the UAMS Graduate School and the IDeA Networks of Biomedical Research Excellence (INBRE) program.
“We want to help prepare a new generation of researchers to solve the problems of tomorrow, especially in light of the pandemic in which science played a critical role in putting us on a path to recovery. Last year, there was high interest and participation that reached pre-pandemic levels,” said Grover Paul Miller, Ph.D., a professor in the College of Medicine Department of Biochemistry and Molecular Biology and the organizer of the symposium.
The 2023 symposium was the second consecutive year for the event following a two-year interruption due to the COVID-19 pandemic.
The event was held July 26 at the I. Dodd Wilson Education Building and backed by grant funding from the National Institute of General Medical Sciences. This time, there was over 130 student researchers registered with more than 100 faculty and administrators in support.
Undergraduate and high school students participated in 17 different research programs in colleges and universities, as well as the U.S. Food & Drug Administration’s National Center for Toxicological Research (NCTR) near Pine Bluff.
“This year is our largest number of student presenters,” Miller said in his opening. “Real research happens when you get to talk about the science you do, because it’s a lot of fun. There are a lot of things that work out really well, and a lot of things that do not. Science is about that journey, and this symposium is about talking about your journey to this day.”
The following students were selected to give oral presentations, which were divided into morning and afternoon sessions:
“These 12 were selected out of 45 submissions,” said Samantha Kendrick, Ph.D., a professor in the College of Medicine Department of Biochemistry and Molecular Biology. “I think they all did a fantastic job.”
Lu, one of the high school students participating in UAMS’ summer research programs, spoke on glioblastoma.
“Glioblastoma is a very common and aggressive type of brain cancer,” Lu said. “Treatment is limited to surgery, radiation therapy and chemotherapy. The problem with glioblastoma is that after treatment, the cancer will almost always come back due to the presence of cancer stem cells.”
Vollintine’s project was “The Effects of Sleep Deprivation on Problem Solving with Artificially Induced Schooling,” with research done using fish.
“Fish are fed twice daily at scheduled times during the five days of testing,” said Vollintine. “The population being tested are fed during and after testing, then returned to regular feeding and regular sleep cycles. LED lighting was used to induced sleep deprivation. The sleep-deprived males were not as inclined to be social.”
Morning and afternoon poster sessions of approximately one hour each gave students a chance to discuss their research with faculty, guests, mentors and peers.
Carter Bierbaum of the University of Central Arkansas and his cohorts in the Summer Undergraduate Research Fellowship program studied the effects of olanzapine, a drug used to treat mental disorders, and its interaction with other medications.
“For drug interactions right now, it’s either yes or no as to whether they can be taken together,” Bierbaum said. “You can say these three drugs can’t be used in combination with each other, but if we had more data maybe it’s just one drug that causes the issue.”
Alasiah Bledsoe of Emory University and the Summer Research Internship Program conducted a review of telehealth definitions.
“We’re trying to show exactly what telehealth is,” said Bledsoe. “Many are using telemedicine and telehealth interchangeably. Telemedicine is provider to provider and patient care, while telehealth encompasses health education, health administration, and public health.”
Ouachita Baptist University’s Lawrence Davis’ research was understanding how organisms move better during long-term space travel.
“We’re looking at the effects of light and hypo-gravity on the development and movement of slime mold,” Davis said. “A slime mold is considered a model organism that has characteristics of animals, fungi and plants. We’re limited on light in space, so we need understand how plants react.”
Trying to find a better way to forecast the maximum rate of oxygen in children was another research topic.
“It’s easy to predict that in adults because it takes several different fitness tests and adults have more control over their bodies,” said Vera Kanu of Hall STEAM High School and the Summer Research Internship Program. “It’s unpredictable in kids, and we want to be able to do one or two fitness tests to be able to predict that maximum rate.”
Guest speaker Sarah Eddy, J.D., Ph.D., an associate at Norton Rose Fulbright in Austin, Texas, talked about “The Unexpected Path from Proteins to Patents & Some Lessons Learned Along the Way.” Eddy, a native of Bigelow, Arkansas, is a former participant in INBRE and attended UAMS’ Graduate School.
Ten students were acknowledged for the top poster presentations:
“These students were selected out of 118 posters,” Miller said. “That’s a significant achievement. There’s a lot of great research out there, and it was highly competitive.”
Diane McKinstry, INBRE summer program manager, received a surprise award.
“She makes time for this symposium every year,” said Miller. “She’s instrumental in keeping a lot of these programs together.”
The day ended with a presentation to Miller for his work.
“This is a fantastic program and I’m thrilled with the way it’s developed over the years,” said Kevin Raney, Ph.D., a professor and chair of the College of Medicine Department of Biochemistry and Molecular Biology. “Dr. Miller is dedicated to excellence in teaching, mentoring, and inspiring the next generation of biomedical scientists. This symposium is a huge success because of him.”
Congratulations to Katie Bronson on the successful defense of her dissertation entitled, “Regulation of Musashi-dependent translational activation by co-associated proteins.” Katie was mentored by Angus MacNicol. She will be staying at UAMS for postdoctoral studies in the lab of Alan Tackett.
Editorial: Advancements in computational studies of drug toxicity.
Flynn NR, Miller GP, Swamidass SJ.
Front Pharmacol.
Katie is a fifth year student in the Biochemistry and Molecular Biology Ph.D program.
She attended Liberty University where she completed a Bachelor of Science degree in biology with a minor in chemistry
My research focus is on the conserved RNA-binding protein Musashi, the proteins it associates with, and the effect those associations have on regulating translation. Musashi is a biomarker for stem cells, regulating asymmetrical differentiation and maintaining a stem cell population. Originally studied as a translational repressor, the MacNicol lab has found that Musashi is required for the translational activation of specific transcripts. However, while Musashi uses its two N-terminal RNA-recognition motifs to bind to RNA, its C-terminus is disordered and contains no enzymatic or catalytic domains. Therefore, Musashi must require protein interactions in complexes to regulate translation, the composition of which could regulate Musashi-dependent translational effects. One of those proteins is Lsm14B. We are one of the first labs to identify Lsm14B as a translational activator, and the first group to identify the Musashi:Lsm14B interaction to be necessary to translate Mos and Cyclin B5 proteins in Xenopus oocytes to re-initiation of the cell cycle as well as translating the pituitary development-specific transcription factor Prop1. I have also discovered over 200 proteins that likely associate with Musashi independent of RNA in the mouse anterior pituitary through immunoprecipitations and mass spectrometry. My research will lay the groundwork for future investigations into the regulation of Musashi-bound RNA transcripts due to Musashi-protein interactions.
Being a Ph.D. student is already a unique experience – a global pandemic in the middle of your Ph.D. truly makes it even more unique. The amount of personal growth I have experienced not only through the usual Ph.D. experience but also through these universally trying times has affected my approach to science and my research goals, highlighting the need for good science and excellent communication.
I will be expanding my research training and experience through a post-doctoral research position here at UAMS.
I would love to learn how to conduct bioinformatics analyses.
I joke that I’m preparing my retirement hobbies – I love gardening, crochet, reading, and tennis. A goal of mine is to have a library of books I’ve already read.
