{"id":8093,"date":"2022-05-27T10:18:55","date_gmt":"2022-05-27T14:18:55","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/compbiomed\/?page_id=8093"},"modified":"2024-01-03T10:12:15","modified_gmt":"2024-01-03T15:12:15","slug":"ignaty-leshchiner","status":"publish","type":"page","link":"https:\/\/www.bumc.bu.edu\/compbiomed\/ignaty-leshchiner\/","title":{"rendered":"Ignaty Leshchiner, Ph.D."},"content":{"rendered":"
\n

\"\"<\/p>\n

Assistant Professor of Medicine
\n<\/b><\/span><\/p>\n

Affiliated Faculty, Broad Institute of MIT and Harvard<\/span><\/p>\n<\/div>\n

Lab website: www.leshlab.org<\/a><\/div>\n
<\/div>\n

\nEducation<\/span><\/strong><\/div>\n
\n
Postdoctoral Fellow, Computational Biology,\u00a0Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, MA\u00a0<\/span>(Profs. Sunyaev and Goessling), 2010-2013<\/span><\/div>\n
\n
Ph.D., Chemistry,\u00a0<\/span>Moscow State University, Moscow, Russia, (<\/span>Profs. Shibaev and Boiko), 2006-2009<\/span><\/div>\n
Visiting Graduate Student, Chemical Engineering, Massachusetts Institute of Technology,\u00a0Langer Lab,\u00a02006
<\/span><\/div>\n<\/div>\n
M.S., Chemistry,\u00a0Moscow State University, Moscow, Russia,\u00a02001-2006,\u00a0summa cum laude<\/i><\/span><\/div>\n
<\/div>\n

\nContact Information<\/strong><\/div>\n
\n

Email:<\/strong>\u00a0<\/span>igleshch@bu.edu<\/p>\n

Office:\u00a0<\/span>K404<\/span><\/p>\n

Research Interests<\/span><\/h4>\n

Computational biology and cancer bioinformatics.<\/span>\u00a0Research in the lab is focused on applying new genomic technologies, computational analysis and AI methods on data from patients\u2019 tumors to understand the biology behind tumor development, treatment evasion, and progression to metastasis. We are developing and applying<\/span>\u00a0tools for simultaneous analysis of multiple samples from the same patient, clonal structure\u00a0<\/span>(PhylogicNDT)<\/span>,<\/span>\u00a0integration of single cell genomics and\u00a0<\/span>transcriptomics, reconstruction of cell subpopulations, their growth kinetics and expression, tumor micro-environment effects,\u00a0<\/span>estimation of order of events (\u201ctiming\u201d) during tumor development and progression. We work with<\/span>\u00a0pre- and post- treatment samples, autopsies\u00a0<\/span>and longitudinal blood biopsies in solid and blood malignancies.\u00a0<\/span><\/p>\n<\/div>\n

\n

Multiomic Technology Development.\u00a0<\/span><\/strong>Integration of multi-modal data\u00a0(genomic, transcriptomic, proteomic, imaging and single cell)\u00a0<\/span>obtained from patients opens up a new era of computational analysis. We are developing tools and technologies to analyze and improve\u00a0<\/span>single cell\/nuclei RNA, DNA and ATAC sequencing, interpret spatial imaging and\u00a0spatial\u00a0transcriptomic datasets, patients’ medical records and radiographic data.<\/span><\/p>\n

Predicting Treatment Response.\u00a0<\/b><\/span>Distant tumor sites\u00a0often respond to treatment and grow at\u00a0<\/span>varying rates, which suggests multiple resistance mechanisms evolving at the\u00a0<\/span>same time in one patient. Understanding subclonal dynamics and relationships is<\/span>\u00a0key for identifying and studying independently resistant cell subpopulations and their deferential response to\u00a0<\/span>chemo-, immuno- or targeted<\/i>\u00a0therapy<\/span>.\u00a0<\/span>We develop methodologies to discover and monitor\u00a0<\/span>evolution of multiple simultaneous resistance mechanisms in a patient,<\/span>\u00a0study short- and long-term dynamics and phenotypes of subclonal cell\u00a0<\/span>populations before and during treatment, early response detection and understanding the differential treatment\u00a0<\/span>response of subclones, including\u00a0<\/span>dynamics of response and recurrence under drug pressure and\u00a0<\/span>transcriptional changes upon drug exposure.<\/span><\/p>\n<\/div>\n

\n

Selected Publications<\/span><\/h4>\n

Leshchiner, I.*<\/strong>, Mroz, E.*, Cha, J.*, . . . Getz, G., Rocco W. Inferring early genetic progression in cancers with unobtainable premalignant disease. Nat Cancer<\/strong><\/em>, 2023;4(4):550-563. doi: 10.1038\/s43018-023-00533-y.\u00a0PubMed\u00a0PMID: 37081260;\u00a0PubMed\u00a0PMCID: PMC10132986.<\/p>\n

Parry, E. *, Leshchiner, I.*<\/strong>, Gui\u00e8ze R *, . . . , Getz, G., Wu, C.J. Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome. Nat Med<\/strong><\/em>, 2023, 29; 158\u2013169 doi:10.1038\/ s41591-022-02113-6. PMID: 36624313.<\/p>\n<\/div>\n

Dentro, S. C.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Haase, K.*, Tarabichi, M.*. . . Loo, P. V. (2021). Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell<\/strong><\/em>, 184 (8), 2239-2254. doi: 10.1016\/j.cell.2021.03.009<\/p>\n

Gerstung, M.*, Jolly, C.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Dentro, S. C.*, Gonzalez, S.*, Rosebrock D., . . . Loo, P. V. (2020). The evolutionary history of 2,658 cancers. Nature<\/strong><\/em>, 578 (7793), 122\u2013128 doi:10.1038\/s41586-019-1907-7<\/p>\n

Parikh, A. R.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Elagina, L., Goyal, L., . . . Corcoran, R. B. (2019). Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med<\/strong><\/em>, 25(9), 1415-1421. doi:10.1038\/s41591-019-0561-9<\/p>\n

Gruber, M.*, Bozic, I.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Livitz, D.*, Stevenson, K., Rassenti, L., . . . Wu, C. J. (2019). Growth dynamics in naturally progressing chronic lymphocytic leukaemia. Nature<\/strong><\/em>, 570(7762), 474-479. doi:10.1038\/s41586-019-1252-x<\/p>\n

Nissim, S.,\u00a0<\/span>Leshchiner, I.,<\/b>\u00a0<\/span>Mancias, J. D., Greenblatt, M. B., Maertens, O., Cassa, C. A., . . .Goessling, W. (2019). Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. Nat Genet<\/strong><\/em>, 51(9), 1308-1314. doi:10.1038\/s41588-019-0475-y<\/p>\n

Stewart, C.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Hess, J., & Getz, G. (2018). Comment on “DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification”. Science,<\/strong><\/em> 361(6409). doi:10.1126\/science.aas9824<\/p>\n

Fishbein, L.*,\u00a0<\/span>Leshchiner, I.*<\/b>, Walter, V.*, Danilova, L., Robertson, A. G., Johnson, A. R., . . .Wilkerson, M. D. (2017). Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell<\/strong><\/em>, 31(2), 181-193. doi:10.1016\/j.ccell.2017.01.001<\/p>\n

Shaw, A. T., Friboulet, L.,\u00a0<\/span>Leshchiner, I.<\/b>, Gainor, J. F., Bergqvist, S., Brooun, A., . . . Engelman, J. A. (2016). Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med,<\/strong><\/em> 374(1), 54-61. doi:10.1056\/NEJMoa1508887<\/p>\n

L<\/span>es<\/span><\/b>hchiner, I.<\/b>, Alexa, K., Kelsey, P., Adzhubei, I., Austin-Tse, C. A., Cooney, J. D., . . . Sunyaev, S. R. (2012). Mutation mapping and identification by whole-genome sequencing. Genome Res<\/strong><\/em>, <\/span>22(8), 1541-1548. doi:10.1101\/gr.135541.111<\/span><\/p>\n

Full list of publications:<\/span><\/p>\n<\/div>\n

https:\/\/www.ncbi.nlm.nih.gov\/sites\/myncbi\/1n7cl6WQD8vA-\/bibliography\/51720242\/public\/?sort=date&amp;direction=descending.<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"

Assistant Professor of Medicine Affiliated Faculty, Broad Institute of MIT and Harvard Lab website: www.leshlab.org Education Postdoctoral Fellow, Computational Biology,\u00a0Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, MA\u00a0(Profs. Sunyaev and Goessling), 2010-2013 Ph.D., Chemistry,\u00a0Moscow State University, Moscow, Russia, (Profs. Shibaev and Boiko), 2006-2009 Visiting Graduate Student, Chemical Engineering, Massachusetts Institute of Technology,\u00a0Langer Lab,\u00a02006 M.S., Chemistry,\u00a0Moscow […]<\/p>\n","protected":false},"author":16142,"featured_media":0,"parent":0,"menu_order":3,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/pages\/8093"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/users\/16142"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/comments?post=8093"}],"version-history":[{"count":13,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/pages\/8093\/revisions"}],"predecessor-version":[{"id":8615,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/pages\/8093\/revisions\/8615"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/media?parent=8093"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}