rama krishnaProfessor

Research Areas
Protein structural biology


Biography

N. Rama Krishna is a Professor in the Department of Biochemistry and Molecular Genetics, focusing on protein structural biology and the development of novel NMR techniques useful in drug discovery research (see Research Interests below). He received his Ph.D. degree in Physics (Nuclear Spin Relaxation of Coupled Systems in Liquids by Double Resonance) from the Indian Institute of Technology-Kanpur in India in 1972. He holds joint appointments in the Comprehensive Cancer Center, CAMBAC, and the Department of Chemistry. In 1984 he assumed the Directorship of the NMR Facility of the UAB Comprehensive Cancer Center, and upgraded its research capabilities through several NSF and NIH Instrumentation Grants (including a NCRR High End Instrumentation Grant for $2 million approved in 2008 and awarded in January 2009). In 2011 he has successfully established the State-of-the-Art Central Alabama High-Field NMR Facility with a Bruker-Biospin 850 MHz NMR system as its center piece, flanked by 600 MHz and 500MHz NMR systems.  After serving as the Director of the High Field NMR Facility for over 32 years and successfully renewing the peer-reviewed NCI grant support to the NMR Facility for 35 years through seven competing renewal applications of the CCSG grant P30CA013148 of the Cancer Center, Dr. Krishna stepped down from that position at the end of 2016 to focus on drug discovery research.

Outside Interests include 18th and 19th century copper plate engravings, stone lithographs and chromolithographs primarily depicting the original art of John James Audobon, John Gould and other ornithologists, fine art (renaissance art, and Asian religious sculpture), classical music, art museums, historic sites, hiking, and ethnic cuisines.


Research Interests

Krishna laboratory is primarily interested in biomolecular NMR spectroscopy, protein structural biology, and drug design. Recent work has centered around structure/function investigations in proteins and the development of NMR methodologies for determining the structure refinement of proteins and protein/ligandcomplexes.

During the past three decades at UAB, Krishna laboratory made many significant contributions to our understanding of the structural biology of a large number of biologically significant proteins and complex carbohydrates. These include the sodium channel-binding long-chain neurotoxins from the venom of the North American scorpion Centruroides sculpturatus Ewing, and a potassium channel blocking toxin from the venom of the Brazilian scorpion Tityus serrulatus, proteins from HIV-1 and bacteriophage P22 viruses, and connective tissue proteoglycans, among others. Current drug discovery work is aimed at developing inhibitors of a Fas-induced survival signaling pathway by which pancreatic cancer cells escape apopotosis and proliferate. In initial studies, Krishna laboratory has identified some promising small molecule leads that exhibit anti-proliferation activity against Mia Paca2, BxPC3, and AsPC1 cell lines. Current efforts are directed at structure-based design and development of these lead compounds using a multidisciplinary approach. If successful, these inhibitors of the Fas-induced survival signaling will likely contribute to novel approaches in combination therapiesto treat this deadly form of cancer.

Krishna laboratory also has an active interest in developing NMR-based structure-refinement procedures. He introduced to the biomolecular NMR community in 1978 the NOE R-factor and the Complete Relaxation Rate Matrix methods for use in protein structure refinements. In collaboration with Drs. Istvan Sugar and Yuan Xu, he has developed a variable target intensity-restrained global optimization (VARTIGO) procedure and Metropolis Simulated Annealing (MSA) refinement of dihedral angles procedure using experimental NOESY intensitiesas constraints. Another major contribution involved the development of a Complete Relaxation and Conformational Exchange Matrix (CORCEMA) procedure for interpreting the NOESY spectra of interacting molecules such as complexes of reversibly forming ligand-receptor complexes. The CORCEMA theory is very general and is applicable over a wide range of binding constants for the complex (weak binding to tight binding), and is useful for the quantitative interpretation of transferred NOESY data. More recently, his laboratory extended the CORCEMA theory to the saturation transfer difference (STD)-NMR experiment. This theory (CORCEMA-ST) is particularly useful in determining the boundconformations of reversibly binding low molecular weight lead compounds recognized by a target protein. Such information in turn can lead to structure-based design of new drugs. The CORCEMA program is currently being utilized by over 115 different research groups including four major pharmaceutical companies in five different continents in their drug discovery and developmental work. The CORCEMA and CORCEMA-ST programs may be obtained by contacting Dr. Krishna.

Dr. Krishna’s research program has been supported at various times by grants from the NIH (NIAID, NCI, NIGMS, NINDS, NCRR), NSF, American Heart Association, Arthritis Foundation, the Leukemia Society of America, and Pharmaceutical Industry.

Awards and Honors

  • Elected as a Fellow, American Association for the Advancement of Science (AAAS), 2012
  • Served as a member on numerous NIH Study sections (Research Project Grant Applications, Site Visits, NRSA Fellowship Applications (F30,F31,F32), Shared Instrumentation Grants), and as an external reviewer for NSF (Research Projects and Shared Instrumentation Grant Applications).
  • Served as external reviewer for research project grant applications to private foundations in the US, and granting agencies in UK, Austria, and Israel.
  • NCRR High-End Instrumentation Grant for $2 million, 2009
  • Nature Editorial (Nature 452:822-823 (2008)) on the STD-NMR study of receptor recognition by rabbit hemorrhagic disease virus (RHDV) published  in J. Amer. Chem. Soc., 130:3669-3675 (2008).
  • Invited to organize and chair the Mini-Symposium on “Small Molecule-Protein Interactions and Screening by NMR”, SMASH International  Conference,  New Hampshire, Sept 2006
  • Invited Guest Editor for Biological Magnetic Resonance series Volumes 16 (Modern Techniques in Protein NMR, (1998)), 17 (Structure Computation and Dynamics in Protein NMR, (1999)), and 20 (Protein NMR for the Millennium, (2003)).
  • Invited Panel Member, International Conference on “NMR as a Structural Tool: Present Status and Future Directions" IUPUI, Indianapolis, October 30, 1994.
  • Leukemia Society of America Scholar, 1982-87.
  • Senior Research Fellow, CSIR, India,1968-70.
  • Junior Research Fellow, CSIR, India, 1966-68.
  • The “Ramamohana Rao Memorial Prize" For Overall Distinction, M.Sc. Class, 1966, Andhra University, India.
  • “Metcalfe Gold Medal" for being the Top Student in the M.Sc. Degree (Physics) Examination, 1966, Andhra University, India.
  • Indian Atomic Energy Commission National Merit Scholar, 1965, Andhra University, India.

Education

Graduate School
Ph.D., Indian Institute of Technology, Kanpur, India

Contact

Office
McCallum Basic Health Science Building
Room 490
1918 University Blvd.
Birmingham, AL 35294-0005

Phone
(205) 934-5695

Email
nrk@uab.edu

Committed to exploring new frontiers in basic and translational research.

The Department of Biochemistry and Molecular Genetics is an integral part of the vibrant biomedical research community at the University of Alabama at Birmingham (UAB). UAB ranks among the top public institutions of higher education in terms of research and training awards. Research conducted by the faculty, staff, and students of the Department of Biochemistry and Molecular Genetics is currently supported by more than $4.3 million per year in extramural, investigator-initiated grants.

Research

The Department of Biochemistry and Molecular Genetics carries out cutting-edge basic and translational research. Research strengths in the department includes cancer biology, chromatin and epigenetic signaling, metabolism and signaling, regulation of gene expression, structural biology, DNA synthesis and repair, and disease mechanisms.

Education

Graduate students and postdoctoral fellows in the Department of Biochemistry and Molecular Genetics are trained to carry out hypothesis-driven research using advanced research techniques. This training will prepare our graduates for a career in not just biomedical research, but also in other diverse fields that require critical thinking. Our faculty also proudly trains professional (MD, DDS, & DO) students, as well as undergraduate students at UAB.

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