Microbiology and Immunology
Columbia University, College of Physicans and Surgeons
Our research focuses on the mechanism(s) that determine the 3D-structure and organization of the genome. We use genomics, single molecule super resolution microscopy, biochemistry and molecular genetics to address pressing questions. Currently, we are focused on noncoding RNA transcription mediated genome regulation in normal and diseased cellular states.
We envision that through careful, innovative and educated probing of the mammalian transcriptome, we will accumulate sufficient knowledge that will allow us to predict cancer onset and thereby facilitate early intervention treatment.
Uttiya Basu received his PhD in molecular biology from Albert Einstein College of Medicine. After finishing his postdoctoral training which focused on molecular immunology at Harvard Medical School, he joined Columbia University as an assistant professor in the Department of Microbiology and Immunology. His laboratory utilizes technologies involving genome engineering, genomics, biochemistry and in vivo imaging. His research is focused on the various mechanisms by which non-coding RNA transcription controls genome architecture and somatic mutagenesis processes in mammalian cells, especially those of lymphocyte origin. Dr. Basu has been recognized with the Irvington Institute (CRI) fellowship, the Leukemia and Lymphoma Society of America Scholar award, the Leukemia Research Foundation New Investigator award, the Irma Hirschl Fellowship, and the NIH Director’s program Innovator award. In 2016, he was awarded tenure at Columbia University in the City of New York and promoted to Associate Professor.
Infectious Disease Induced DNA Alterations in B Cell Malignancies
B-lymphocytes are well known for their ability to generate antibodies of the highest affinity to neutralize various antigens we encounter. In the process of generating high-affinity antibodies, B cells mutate the immunoglobulin loci (antibody encoding genes) and other regions of the B cell genome. These mutations are catalyzed by the enzyme activation induced deaminase (AID). Sometimes, AID, in its effort to generate genetic diversity in the antibody encoding genes, mutagenizes other regions of the B cell genome that eventually act as genetic lesion responsible for chromosomal translocations that cause cancer.
“The award from PSSCRA allows my laboratory to participate and contribute in the unprecedented revolution that is going on in the field of cancer therapy and prognosis. We plan to use the hidden knowledge present in the noncoding transcriptome of infectious disease induced cancer genomes to predict disease onset and develop therapies. I feel fortunate to be a scientist at a time when the power of genomics, immunotherapy and genome engineering has invigorated the fight against cancer.”
Recent advances in biology have lead to the paradigm shifting discovery that close to 90% of the human and mouse genomes express non-protein coding (nc) RNAs that may have some unidentified biological function. In this grant application, we investigate how AID and the non-coding RNA transcription in B cells combine to aberrantly hypermutate oncogenic DNA sequences following parasitic and bacterial infections. Using mouse genetics, genomics, and biochemistry we aim to investigate how pathogenic infection-stimulated signaling pathways activate transcription of AID and ncRNAs leading to B cell tumorigenesis. Following successful generation of an infection-induced B cell lymphoma model, antibody- and chemotheurapeutic-induced inhibition of AID and B cell lymphomagenesis could be assessed for development of anticancer therapy. B cell lymphomas are one of the primary cause of human cancer in the United States and in the rest of the world (including in sub-saharan Africa, where Burkitt lymphoma is endemic), thus our studies have direct relevance in understanding, identifying, and curing cancer.
“The courage and ability to follow one’s boldest ideas to identify solutions that gives hope for cure of the worst of diseases is innovative science for me. Innovative science tends to be outside the realms of conventional wisdom and techniques, and requires the best from dedicated individuals with brilliant minds.”