Spatiotemporal Regulation of Chemokine PolarityI am interested in understanding how the spatiotemporal organization of the chemokine system is networked with inflammatory responses to operate together and perform diverse functions that lead to chronic disorders such as atherosclerosis. As drivers of the inflammatory response, chemokine(s) and chemokine receptors mediate this process by regulating the migration of the various leukocyte subsets through diverse G protein coupled receptors [GPCRs]. We are looking at both proximate and evolutionary basis of diseases as it applies to injury, wound healing and repair. Course Director – Evolutionary Medicine in Health and DiseaseEvolutionary medicine provides an alternate way to look at health and disease. Inflammation, resistance, virulence and diseases are consequences of selective pressure and compromises incurred by organisms across evolutionary timescales. Understanding this dynamics of natural selection may help explain the complexity of human disorders. This course offers an integrated approach to study biological histories and conflicts that have shaped all life forms, by using the principles of evolution as they apply to medicine and public health. This course will address the elements of evolutionary theory, interpretation of data in relation to specific hypotheses, major human infectious, chronic, and genetic diseases, in an evolutionary perspective.

Assistant Professor of BiochemistryIdentified the role of CC Chemokine CCL-1 responsive gene expression profile in human HeLa cells

Show that that CC chemokine receptor CCR8 mediates human vascular smooth muscle cells (VSMCs) chemotaxis and matrix mettaloprotein- 2 [MMP-2] secretion. The induction of CCR8 and CCL1/TCA3 under conditions associated with VSMC proliferation and migration raises the possibility that CCR8 may play an important role in vessel wall pathology.

Identified CC Chemokine CCL1 and CCR-8 in Kaposi sarcoma showing that CCR8 may modulate endothelial function : Identified CCR8 and I-309 (CCL1) on the endothelium of human atherosclerotic plaques and in endothelial-derived spindle cells of Kaposi sarcoma. Developed transgenic and knockout animal mouse models: Role of CCR8 during vascular injury were studied on mouse models subjected to injury of femoral artery. Development of inhibitors: (i) Monoclonal antibodies against the chemokine receptor CCR8; (ii)Designed and characterized chemokine specific siRNA and (iii) Established CCR8 deficient cell lines.

Identified CC chemokine I-309 ( CCL1 ) as a major chemoattractant in Lipoprotein(a) [Lp[a)] mediated atherosclerosis : Human endothelial cells treated with Lipoprotein (a) result in the expression of a chemokine I-309 (CCL1) This resulted in the funding of an NIH RO1 grant.Lab Head : Peter Harpel,MD/PhD

Determined how the regulation of transcription factor AP - 1 activity is mediated by AML / ETO : The t (8;21) translocation is the most frequent genetic abnormality associated with acute myelogenesis leukemia. Based on the hypothesis that AML and AML / ETO function as transcription regulators of certain genes which in turn trigger signal pathways leading to changes in AP- 1 activity, we found that AML / ETO fusion protein raises activity in MLA 144 cells and the zinc finger motif is required for this activity. Supervisor : Stephen D. Nimer, MD/PhD

Isolated and characterized Myelin Regulatory factor ( MRF - 1) : Isolation of a novel cDNA myelin regulatory factor - 1 was derived from a mouse brain expression library which has 97% homology with the previously identified splicing factor SC35.MRF-1; increases transcription of the MBP promoter in glial cells and this activation requires an intact MRF – 1 binding site within the MB3 region. Identified a distal cis - acting regulatory element in myelin basic protein gene promoter : Identified the G residues located between -93 to -130 nucleotides with respect to the RNA start site in the myelin basic protein gene and contains a binding site for the NF1 / CTF family of transcription are important to confirm transcriptional activity to this domain in transiently transfected glial cells.  Determined the expression of myelin basic protein (MBP) in transgenic mice expressing human neurotropic virus, JCV : Programmed expression of JCV T-antigen, which overlaps the MBP gene transcription at early stages of myelination, suggests the involvement of a pathway which modulates stage specific regulation of myelin genes and viral gene expression in transgenic mice during brain development. Supervisor : Kamel S. Khalili,Ph.D

Developed the fist transgenic fish in India and accomplished our objective of integrating the foreign growth hormone gene in Indian major carp Labeo rohita genome. Established a aquaculture station at Dhauj, India for all field work related to the project.Collaborators: Dr Jaspal S. Khillan, Prof. PG Talwar Funding Source: Department of Biotechnology, Government of India

Expedition aboard NIO research Vessel Gavashini to Laccadive islands led to the identification of fish species from Laccadive Island which added to the existing knowledge of fish collection on the island. Expedition Leader : Dr. MVM Wafar,NIOFunding : Department of Ocean Development, Government of India.