Igor M. Leykin, M.D., Ph.D.
Dr. Leykin is an Investigator in the Section on Vascular Cell Biology, Bioinformatics Core Manager at Joslin and Instructor in Medicine at Harvard Medical School. He received his medical degree from Vitebsk State Medical University in Belarus and his doctoral degree in immunology at the Weizmann Institute of Science in Israel. Dr. Leykin did a clinical residency in psychiatry at the Mental Health Center Beer-Yakov, Israel. He then went on to do research fellowships at Massachusetts General Hospital in Immunology and in Bioinformatics at the Harvard School of Public Health.
Autoimmunity—the loss of immune “self” tolerance—is responsible for a range of human diseases; type 1 diabetes is the result of autoimmunity directed against the insulin-producing beta cells of the pancreas. Dr. Leykin studies ways of reversing autoimmunity with bone marrow transplantation (BMT) in a mouse model of type 1 diabetes. BMT is widely used to treat leukemia and other diseases that arise from defects in blood production. Using bone marrow from diabetes-resistant donor mice, Dr. Leykin has had great success at restoring beta-cell tolerance in diabetic mice via two different BMT techniques: myeloablative (which completely replaces the recipient’s bone marrow and immune system) and nonmyeloablative.
Complementing his diabetic studies, Dr. Leykin is investigating whether neuroleptic drugs used to treat schizophrenia (which some believe to have an autoimmune component) have immunosuppressive features. His laboratory (in vitro) and animal (in vivo) studies of immune cells (lymphocytes) have shown that haloperidol and clozapine, two of the most commonly prescribed antischizophrenic drugs, do suppress immune cell function. Also, he has found that the lymphocytes of schizophrenic patients are highly sensitive to a protein called heat shock protein 60, which is believed to be a triggering antigen for many autoimmune diseases.
In addition to his immunological efforts, Dr. Leykin is researching ways to enhance the utility of data collected using genomic technologies. Single nucleotide polymorphisms (SNPs) are small genetic alterations that account for the vast majority of the variation across the human genome. The oligonucleotide SNP array (or “SNP chip”) has become an indispensable tool for SNP-based genetic studies, particularly since certain SNPs are strongly linked to human disease. Dr. Leykin has developed software that formats SNP array data for analysis using a range of computational tools.
Separately, to better understand the structure, function and location of promoters (stretches of DNA located upstream of genes that help improve binding of the cell’s transcriptional proteins), Dr. Leykin has mapped all transcription start sites within the human and mouse genomes using expressed sequence tags (ESTs; short DNA sequences that flag gene positions). From there, he has extracted DNA sequences just upstream of the transcription start sites; these sequences correspond to each gene’s respective promoter. Dr. Leykin has compiled a database of the promoter sequences generated, and developed software tools to search for and analyze genes that use common promoters.
Selected References
Leykin I, Kao MC, Wong WH. HumanUpstream and MouseUpstream, databases of promoter sequences in the human and mouse genomes. OMICS 9:220-224, 2005.
Leykin I, Hao K, Cheng J, Meyer N, Pollak MR, Smith RJ, Wong WH, Rosenow C, Li C. Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data. BMC Genet 6:7, 2005.
Nikolic B, Takeuchi Y, Leykin I, Fudaba Y, Smith RN, Sykes M. Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity. Diabetes 53:376-383, 2004.
Koeller KM, Haggarty SJ, Perkins B, Leykin I, Wong JC, Kao MCJ, Schreiber SL. Chemical genetic modifier screens: small molecule trichostatin suppressors as probes of intracellular histone and tubulin acetylation. Chem Biol 10:397-410, 2003.
Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ. Extensive and divergent circadian gene expression in liver and heart. Nature 417:78-83, 2002.
