Pediatric Hematology and Oncology
Department of Pediatrics, UAMS College of Medicine
Arkansas Children’s Research Institute
What is your relationship to cancer?
As described by Dr. Siddhartha Mukherjee in his Pulitzer Prize winning monograph, cancer is and continues to be “The Emperor of All Maladies”. Being diagnosed with cancer is always scary for obvious reasons. Not only it is difficult to diagnose, treat and experience, it is also difficult to describe. Cancer is not one disease, but a collective name for what can happen when our body’s chemical instruction manual goes wrong.
I have my training and experience in biological engineering and had no concrete plan to pursue cancer research. During my training at the Cancer Institute, I first came in close contact with cancer patients, while sharing the elevators or getting foods at the cafeteria. I was deeply saddened to see the painful faces, their struggle to walk freely like a healthy individual, and a silent fear in the eyes of their family. This gradually changed my perception and motivated me to steer my interest to cancer research where my efforts and skillset could ultimately have an important impact in the lives of cancer patients and their families.
What do you hope to contribute as a member of the Winthrop P. Rockefeller Cancer Institute?
Arkansas Children’s Research Institute and UAMS provided me with a unique opportunity to invest my interest in pediatric leukemia research, which also allows for broadening the scope for cancer research in Arkansas. Dynamic collaborative efforts between the institutes are also supportive of the goal of the Winthrop P. Rockefeller Cancer Institute in achieving National Cancer Institute designation. I would like to contribute to the institutional goal and vision by publishing our innovative research, strengthening collaborative efforts and obtaining competitive research fundings. I am also highly motivated to host trainees at the undergraduate, graduate or advanced level in our laboratory and have them acquire critical assets, including knowledge, skills, and interest in cancer research.
Tell us about your current research?
Our laboratory presently focuses on a deadliest subtype of pediatric acute myeloid leukemia (AML). Although AML impacts all ages, AML with the ETO2-GLIS2 fusion oncoprotein is a unique entity of early childhood (< 3 years). Infants and young children with this type of AML have among the worst outcomes of all pediatric AML subtypes. The fusion between ETO2 and GLIS2 occurs due to an inversion event at chromosome16, which is not detected by routine cytogenetics and thus must be specifically sought by fluorescent in-situ hybridization technique or molecular studies, likely explaining its late and recent discovery. Whole genome sequencing studies have failed to identify additional second hit coding gene mutations in these cases and the overall mutational burden is among the lowest of all human cancers.
In contrast, laboratory stem-cell models show that introduction of the fusion alone is sufficient for malignant transformation. Thus, ETO2-GLIS2 AML is suspected to be critically supported by epigenetic mechanisms, however these have not been adequately investigated. Previous literature suggests that ETO2-GLIS2 induce havoc changes in chromatin architecture and preferentially activates H3K27ac marked chromatin at atypical (neo) gene loci, which are defined as super-enhancers (SE) that are supportive of sustenance of leukemic gene expression.
Based on previous literature and our preliminary data, we identified that mediator (MED) 12 like (MED12L) protein is epigenetically enhanced and overexpressed in ETO2-GLIS2 positive AML subgroup, and co-upregulated with CDK8 of the MED-kinase module. Given ETO2-GLIS2 and MED12L mutually occupies the neo-SE element, and MED proteins aid in formation and sustenance of SE activities in cancer, we aim to investigate the (1) MED12L interactions with ETO2-GLIS2 bound or unbound to SE associated proteins and determine (2) whether epigenetic perturbations of MED12L can impair aberrant transcriptional machinery and overall leukemic growth. Our studies are expected to develop novel insights into changes in chromatin architecture and mediator-enhancer mechanisms, favoring leukemic growth, which may be relevant to other AML subtypes and hematological malignancies.
A native of Calcutta, India, Dr. Choudhury earned bachelor’s and master’s degrees from the University of Calcutta. He received a Ph.D. in biotechnology from the Indian Statistical Institute, during which time he received multiple senior research fellowship awards and a postdoctoral fellowship in nano science and technology. In 2013, he was awarded a three-year postdoctoral fellowship from the W.M KECK Foundation at Purdue University to study in the laboratory of Professor Joseph Irudayaraj. He joined the UAMS Myeloma Center as a research associate in 2013 and was promoted to assistant professor in the Department of Pediatrics in 2020. He is a member of the Cancer Institute’s Cancer Biology Research Group. He received a 2020-2021 UAMS Seeds of Science Award. His work is widely published in such journals as Blood Cancer Journal, Cancers, Cancer Research Cells, Journal of Hematology & Oncology, Scientifics Reports, and Oncotarget.