Biochemistry and biophysics: transcription, signaling, pre-mRNA splicing, mRNA transport, protein-protein, protein-DNA and protein-RNA interactions
Albert Einstein University
Albert Einstein University
St. Xavier's College
Our research focuses primarily on the detailed mechanisms of signaling pathways that lead to the regulation of gene expression by nuclear factor ºB(NF-ºB). We have recently initiated a second project that aims to understand mRNA processing and transport. The foundation of our research rests upon high resolution x-ray structures of proteins and protein complexes. Hypotheses derived from these three dimensional structures are tested through biochemical and biological experiments to provide greater functional understanding of these important regulatory processes.
In most cells NF-º B dimers are retained in the cytoplasm due to their association with a family of inhibitor proteins called the I ºBs. Various stimuli trigger a series of phosphorylation reactions that ultimately activate specific Iº B kinase complexes (IKKs). Phospho-I ºB is degraded by the ubiquitin-linked proteasome pathway, resulting in free Rel/NF-ºB dimers. These dimers then translocate to the nucleus and bind to specific DNA targets to induce transcription. Involvement of multiple family members of NF-ºB, IºB and IKK in a differential manner adds complexity to this signaling pathway. We are interested in determining the mechanism of a) NF-ºB dimer formation, b) regulation of NF-º B by Iº Bs, c) IKK regulation, d) ubiquitination of IºBs and e) transcriptional regulation by NF-ºB.
Serine/arginine rich proteins (SR proteins) are essential for pre-messenger RNA processing and possibly for mRNA transport from the nucleus to the cytoplasm. SR proteins are modular in nature, containing an N-terminal RNA binding domain and C-terminal domain rich in SR/RS dipeptides. Phosphorylation of the serines of the RS dipeptides is essential for splicing and transport activities of the SR proteins. A novel class of kinases known as SR protein kinases (SRPKs) specifically phosphorylate these serines. We are interested in structure/function studies of the SR proteins and SRPKs in both yeast and mammalian systems.
Primary Research Area
Activity within UCSD: When I was directly involved in graduate student admission and recruitment in our department, I spent a significant amount of time to recruit minority students by attending Society for Advancement of Chicanos and Native Americans in Science (SACNAS) meetings so that minority students would be encouraged to join our graduate school. I have had students in my group from the Minority Access to Research Career (MARC) and McNair programs. Served as a mentor to the students of the American Chemical Society (ACS). Six of nearly fifty undergraduate students trained in my laboratory are of Hispanic origin. Two minority graduate students joined my group and one is now a facluty member at the University of Georgia.
Activity outside the US: I visit India two to three times a year during UCSD academic breaks. For many years I have been involved in promoting education among disadvantaged students in rural areas in the state of West Bengal in India. I particularly pay attention to two schools and a tutorial with unique characteristics: one school is an all girls’ school and the other is located in a poverty stricken area where the parents of over 50% of the students are daily laborers with no formal education. I visit these schools two to three times a year, coordinating with teachers to identify talented students to ensure that these students can have a college education. Some of these students are now in the medical, engineering and business schools. The tutorial, managed by a non-profit organization, is for over one hundred children from poor families who fall behind in math and science. Several college students tutor these students for a minimal or no fee. Besides education, the organization also provides food for the children. I visit the tutorial once a year and support the organization with funds. My goal is to expand this effort to other rural schools/tutorials in Bengal so that a larger pool of students can be guided in their careers.
I have been teaching short graduate courses in universities/colleges within and around Kolkata, the state capital of West Bengal. I have been doing this since 1996 during my visit to India during the summers. This year I am teaching a short course (RNA biology) to the master students of Lady Brabourne’s college. This is a renowned all girls’ college in India. This is in part of my mission to promote higher education among women in India. I am also teaching a course on ‘Biomolecules’ in Calcutta University.
I visit a non-governmental organization named ‘OFFER’ in Kolkata, India, who shelters, protects and educates HIV infected children. Currently, sixty three children (ages 2 mo to 15 yr) stay in the shelter. I wish to continue to visit and work in the shelter more frequently while I am in the city.
- Mechanism of Iº Ba Binding by NF- ºB Dimers. With C. Phelps, L.L. Sengchanthalangsy, and T. Huxford. J. Biol. Chem. 275, 29840 (2000).
- NF-ºB p65 Uses d Distinct Sets of Residues to Recognize Different DNA Targets. With Y-Q. Chen, L.L. Sengchanthalangsy, and A. Hackett. Structure 8, 419 (2000).
- The Mechanism of the DNA-binding by Rel/NF-ºB Dimers. With C. Phelps, S. Malek, and L.L. Sengchanthalangsy. J. Biol. Chem. 275, 24392 (2000).
- Characterization of the Dimer Interface of Transcription Factor NF-ºB p50 Homodimer. With L.L. Sengchanthalangsy, S. Dutta, D-B. Huang, E. Anderson, and E.H. Braswell. J. Mol. Biol. 289, 1029 (1999).
- The Crystal Structure of Iº Ba /NF-º B Complex Reveals Inhibition of NF- ºB Functions. With T. Huxford, D-B. Huang, and S. Malek. Cell 95, 759 (1998).