Ignaty Leshchiner, Ph.D.

Associate Professor of Medicine (pending)

Affiliated Faculty, Broad Institute of MIT and Harvard

Education

Postdoctoral Fellow, Computational Biology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA (Profs. Sunyaev and Goessling), 2010-2013

Ph.D., Chemistry, Moscow State University, Moscow, Russia, (Profs. Shibaev and Boiko), 2006-2009

Visiting Graduate Student, Chemical Engineering, Massachusetts Institute of Technology, Langer Lab, 2006

M.S., Chemistry, Moscow State University, Moscow, Russia, 2001-2006, summa cum laude

Contact Information

Email: igleshch@bu.edu

Office: K404

Research Interests

Computational biology and cancer bioinformatics. Research in the lab is focused on applying new genomic technologies, computational analysis and AI methods on data from patients’ tumors to understand the biology behind tumor development, treatment evasion, and progression to metastasis. We are developing and applying tools for simultaneous analysis of multiple samples from the same patient, clonal structure (PhylogicNDT), integration of single cell genomics and transcriptomics, reconstruction of cell subpopulations, their growth kinetics and expression, tumor micro-environment effects, estimation of order of events (“timing”) during tumor development and progression. We work with pre- and post- treatment samples, autopsies and longitudinal blood biopsies in solid and blood malignancies.

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

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

Selected Publications

Dentro, S. C.*, Leshchiner, I.*, Haase, K.*, Tarabichi, M.*. . . Loo, P. V. (2021). Characterizing

genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell, 184 (8), 2239-

2254. doi: 10.1016/j.cell.2021.03.009

Gerstung, M.*, Jolly, C.*, Leshchiner, I.*, Dentro, S. C.*, Gonzalez, S.*, Rosebrock D., . . . Loo,

P. V. (2020). The evolutionary history of 2,658 cancers. Nature, 578 (7793), 122–128

doi:10.1038/s41586-019-1907-7

Parikh, A. R.*, Leshchiner, I.*, Elagina, L., Goyal, L., . . . Corcoran, R. B. (2019). Liquid versus

tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal

cancers. Nat Med, 25(9), 1415-1421. doi:10.1038/s41591-019-0561-9

Gruber, M.*, Bozic, I.*, Leshchiner, I.*, Livitz, D.*, Stevenson, K., Rassenti, L., . . . Wu, C. J.

(2019). Growth dynamics in naturally progressing chronic lymphocytic leukaemia. Nature,

570(7762), 474-479. doi:10.1038/s41586-019-1252-x

Nissim, S., Leshchiner, I., 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, 51(9), 1308-1314. doi:10.1038/s41588-019-0475-y

Stewart, C.*, Leshchiner, I.*, Hess, J., & Getz, G. (2018). Comment on “DNA damage is a

pervasive cause of sequencing errors, directly confounding variant identification”. Science,

361(6409). doi:10.1126/science.aas9824

Fishbein, L.*, Leshchiner, I.*, Walter, V.*, Danilova, L., Robertson, A. G., Johnson, A. R., . . .

Wilkerson, M. D. (2017). Comprehensive Molecular Characterization of Pheochromocytoma and

Paraganglioma. Cancer Cell, 31(2), 181-193. doi:10.1016/j.ccell.2017.01.001

Shaw, A. T., Friboulet, L., Leshchiner, I., 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, 374(1), 54-61. doi:10.1056/NEJMoa1508887

Leshchiner, I., 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,

22(8), 1541-1548. doi:10.1101/gr.135541.111

Full list of publications:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1n7cl6WQD8vA-/bibliography/51720242/public/?sort=date&direction=descending.