Aditi Shastri, M.B.,B.S.

At the Shastri Translational Research Laboratory, we are committed to advancing the understanding and treatment of hematopoietic diseases, with a particular focus on myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Our research spans several interconnected areas:

Hematopoietic Stem and Progenitor Cell (HSPC)-Targeted Therapeutics

Emerging evidence suggests that myeloid malignancies originate from leukemic stem cells, with disease progression driven by the persistence and survival of these cells. Our laboratory is developing innovative therapeutic strategies that target HSPCs in myeloid malignancies, with a particular emphasis on the Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway. STAT3 is a critical regulator that is frequently overexpressed in hematologic malignancies and is associated with poor clinical outcomes. We have developed and evaluated several novel STAT3-targeting agents, including antisense oligonucleotides and targeted degraders, in leukemic cell lines, generating promising preclinical results. Our long-term goal is to translate these findings into early-phase clinical trials.

STAT3 Interactions in HSPCs

We are investigating the interactions between STAT3 and key anti-apoptotic proteins, including BCL2 and MCL1, in HSPCs, as well as how these interactions are influenced by the inflammatory bone marrow microenvironment. These studies may identify novel therapeutic strategies to overcome treatment resistance in myeloid malignancies.

Aging-Related Clonal Hematopoiesis (CH)

In collaboration with Dr. Millman and colleagues, we are studying a longevity cohort enriched for centenarians to understand the biological mechanisms underlying healthy aging. Specifically, we are examining the prevalence and spectrum of clonal hematopoiesis (CH) mutations in these individuals and investigating whether exceptional longevity confers protection against pathogenic CH mutations associated with age-related diseases such as cancer, cardiovascular disease, and Alzheimer's disease.

Environmental Health and Myeloid Malignancies

Our laboratory also investigates the impact of environmental health factors on myeloid malignancies through large-scale epidemiologic and genomic analyses. We examine how social, genetic, and environmental exposures—particularly air pollution—influence disease incidence, treatment response, and patient outcomes. Our goal is to generate evidence that informs public health policy and improves outcomes for patients with hematologic malignancies worldwide.

1. Chakraborty S, Morganti C, Zaldana K, Rivera Pena B, Zhang H, Verma D, Gitego N, Ma F, Aluri S, Pradhan K, Gordon-Mitchell S, Mantzaris I, Goldfinger M, Feldman E, Gritsman K, Shi Y, Hubner S, Qiu YH, Brown BD, Khasawneh A, Skwarska A, de Camargo Magalhães ES, Verma A, Konopleva M, Tabe Y, Gavathiotis E, Colla S, Gollob J, Dey J, Kornblau SM, Koralov SB, Ito K, Shastri A. A STAT3 degrader demonstrates efficacy in venetoclax resistant acute myeloid leukemia. Leukemia. 2026 Feb 17. doi: 10.1038/s41375-026-02883-9. Epub ahead of print. PMID: 41703028.
2. Rivera-Peña B, Chakraborty S, Shi Y, Zhang H, Desai SR, Patel PP, Sun Y, Zhao R, Choudhary G, Mitchell SG, Pradhan K, Zhang J, Zhang X, Fu B, Lopez R, Tošić I, Aluri S, Schinke C, Wysota M, King Z, Varshavsky A, Feld J, Carbajal M, Ramachandra N, Verma A, Goldfinger M, Sidoli S, Frank DA, Saunthararajah Y, Shastri A. Pyrimethamine overcomes resistance to hypomethylating agents by reducing de novo pyrimidine synthesis. Exp Hematol. 2026 Jan 31:105382. doi: 10.1016/j.exphem.2026.105382. Epub ahead of print. PMID: 41628794.
3. Verma M, Davidsohn MP, Arends CM, Verma D, Sahu S, Pradhan K, Dehghani SS, Murli H, Jasra S, Aggarwal RK, Zhang H, Wysota M, Hosgood D, Verma A, Jaiswal S, Zou Y, Shastri A. Environmental Pollution Triggers Inflammation In Vivo and is Associated With Higher Risk MDS in an Urban Cohort. Am J Hematol. 2026 Feb;101(2):346-349. doi: 10.1002/ajh.70132. Epub 2025 Nov 11. PMID: 41215735.
4. Verma D, Zeig-Owens R, Goldfarb DG, Kravets L, Pradhan K, Rockwell B, Sahu S, Kelly S, Giricz O, Jasra S, Zou Y, Prophete C, Torres LS, Aluri S, Chakraborty S, Kumari R, Gordon-Mitchell S, Wang J, Silver AJ, South TM, Olmstead SD, Hall CB, Sidoli S, Bender R, Landgren O, Greenberger LM, Wickrema A, Madireddy A, Shastri A, Pietras EM, LaFave LM, Nolan A, Cohen MD, Savona MR, Steidl U, Prezant DJ, Verma A. Elevated Clonal Hematopoiesis in 9/11 First Responders Has Distinct Age-related Patterns and Relies on IL1RAP for Clonal Expansion. Cancer Discov. 2025 Dec 2;15(12):2468-2484. doi: 10.1158/2159-8290.CD-24-1590. PMID: 41031953.
5. Verma T, Sahu S, Pradhan K, Aggarwal R, Gordon-Mitchell S, Jasra S, Dehghani SS, Zhang H, Spodek M, Mantzaris I, Konopleva M, Goldfinger M, Verma A, Hosgood D, Verma D, Shastri A, Zou Y. Cigarette smoking is associated with worse prognosis in myelodysplastic syndromes and hematopoietic alterations in murine models. Leuk Lymphoma. 2025 Oct;66(10):1964-1968. doi: 10.1080/10428194.2025.2513675. Epub 2025 Jun 9. PMID: 40488778.
6. Glushakow-Smith SG, Kaur I, Sidoli S, Hemmati S, Angeles E, Sinclair T, Chakraborty S, Battle A, Ames K, Narayanagari SR, Hyka R, Soto M, Tracy M, Vankudoth J, Kitamura S, Miles L, Steidl U, Shastri A, Verma A, Gritsman K. Exploiting an Epigenetic Resistance Mechanism to PI3 Kinase Inhibition in Leukemic Stem Cells. bioRxiv [Preprint]. 2025 Jul 15:2025.07.11.663968. doi: 10.1101/2025.07.11.663968. PMID: 40791365; PMCID: PMC12338508.
7. Wysota M, Pradhan K, Jacobs S, Rosiene J, Hall C, Downward G, Halberstam Y, Shah N, Hosgood D, Shastri A. Fine particulate matter exposure is linked to worse myeloma outcomes in a diverse urban cohort. Blood Cancer J. 2025 Jul 7;15(1):115. doi: 10.1038/s41408-025-01301-0. PMID: 40619445; PMCID: PMC12230138.
8. Rockwell B, Goldfinger M, Mantzaris I, Shastri A, Saunthararajah Y, Gritsman K, Sica AR, Kornblum N, Shah N, Levitz D, Shapiro LC, Gupta R, Munoz A, Dhawan A, Fehn K, Comas M, Verceles J, Cooper DL, Konopleva M, Feldman EJ, Verma A. Metronomic low-dose regimen of decitabine and venetoclax is safe and reduces monocyte burden in chronic myelomonocytic leukemia. Haematologica. 2025 Jul 17. doi: 10.3324/haematol.2024.287253. Epub ahead of print. PMID: 40671491.
9. Aluri S, Ling T, Fraint E, Chakraborty S, Zhang K, Ahsan A, Kravets L, Poigaialwar G, Zhao R, Pradhan K, Cotton A, Bachiashvili K, Yang JI, Budhathoki A, Agarwal B, Gordon Mitchell S, Carbajal M, Sahu S, Boultwood J, Pellagatti A, Steidl U, Wickrema A, Nandakumar S, Shastri A, Suragani RN, Bowman TV, Crispino JD, Vodala S, Verma A. Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes. J Clin Invest. 2025 May 27;135(13):e189266. doi: 10.1172/JCI189266. PMID: 40424086; PMCID: PMC12208544.
10. Edema U, Liu J, Ma MY, Krishnamurthy K, Choudhuri J, Li X, Marhatta A, Qi X, Ma IR, Wang Q, Shastri A, Goldfinger M, Gritsman K, Sica RA, Mantzaris I, Kornblum N, Konopleva M, Wang Y, Shi Y. Immunophenotypic, genetic, and clinical characterization of adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States. Am J Clin Pathol. 2025 Feb 12;163(2):205-214. doi: 10.1093/ajcp/aqae111. PMID: 39212661.
11. Krishnamurthy K, Shastri A, Wang Y. Intramedullary erythrophagocytosis in myelodysplastic syndrome with heterozygous U2AF1 Q157R variant. EJHaem. 2025 Feb 7;6(1):e1084. doi: 10.1002/jha2.1084. PMID: 39927329; PMCID: PMC11804211.
12. Dehghani SS, Wang Y, Ramesh KH, Cooper D, Verceles JA, Boakye K, Konopleva M, Friedman EW, Shastri A. Atypical chronic myeloid leukemia (CML) with ETV6-ABL1 mutation managed successfully with a third-generation TKI and hematopoietic stem cell transplant. Leuk Lymphoma. 2025 Jan;66(1):147-149. doi: 10.1080/10428194.2024.2403666. Epub 2024 Oct 18. PMID: 39423354.
13. Amaeshi LC, Sofianidi AA, Shastri A, Goldfinger M, Konopleva M, Verma AK, Chaitowitz M, Mantzaris I. A germline FLT3 variant in aplastic anemia. Biomark Res. 2025 Jan 7;13(1):4. doi: 10.1186/s40364-024-00717-3. PMID: 39773519; PMCID: PMC11707911.
14. Mantzaris I, Goldfinger M, Uriel M, Shastri A, Shah N, Gritsman K, Kornblum N, Shapiro LC, Sica A, Munoz A, Chambers N, Dhawan A, Verceles JA, Fehn K, Tirone B, Shah L, Clark S, Zhang C, Kim MY, Cooper DL, Verma A, Konopleva MY, Feldman EJ. Venetoclax plus Daunorubicin and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia: Results of a Phase 1b Study. Blood. 2025 Feb 7:blood.2024026700. doi: 10.1182/blood.2024026700. Epub ahead of print. PMID: 39919267
15. Ben-Crentsil NA, Mohammed Ismail W, Balasis ME, Newman H, Quintana A, Binder M, Kruer T, Neupane S, Ferrall-Fairbanks MC, Fernandez J, Lasho TL, Finke CM, Ibrahim ML, McGraw KL, Wysota M, Aldrich AL, Ryder CB, Letson CT, Traina J, McLemore AF, Droin N, Shastri A, Yun S, Solary E, Sallman DA, Beg AA, Ma L, Gaspar-Maia A, Patnaik MM, Padron E. RNA shielding of P65 is required to potentiate oncogenic inflammation in TET2 mutated clonal hematopoiesis. Cancer Discov. 2024 Aug 27. doi: 10.1158/2159-8290.CD-24-0093. Epub ahead of print. PMID: 39189614
16. Aminov S, Giricz O, Melnekoff DT, Sica RA, Polishchuk V, Papazoglu C, Yates B, Wang HW, Sahu S, Wang Y, Gordon-Mitchell S, Leshchenko VV, Schinke C, Pradhan K, Aluri S, Sohn M, Barta SK, Agarwal B, Goldfinger M, Mantzaris I, Shastri A, Matsui W, Steidl U, Brody JD, Shah NN, Parekh S, Verma A. Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency. J Clin Invest. 2024 Feb 20:e175199. doi: 10.1172/JCI175199. Epub ahead of print. PMID: 38376944.
17. Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, Deeg HJ, Patel PA, Sabloff M, Keating MM, Zhu N, Gabrail NY, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern AE, O'Connell CL, Roboz GJ, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao KH, Oganesian A, Hao Y, Keer HN, Azab M, Savona MR. Oral decitabine-cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. Lancet Haematol. 2024 Jan;11(1):e15-e26. doi: 10.1016/S2352-3026(23)00338-1. PMID: 38135371.
18. Wei JX, Shastri A, Sica RA, Mantzaris I, Kornblum N, Shah U, Janakiram M, Gritsman K, Verma A, Goldfinger M, Cooper D, Shah N. Impact of race and ethnicity on early mortality in multiple myeloma: a SEER analysis. Haematologica. 2023 Oct 26. doi: 10.3324/haematol.2023.283304. Epub ahead of print. PMID: 37881838.
19. Vegivinti CTR, Keesari PR, Veeraballi S, Martins Maia CMP, Mehta AK, Lavu RR, Thakur RK, Tella SH, Patel R, Kakumani VK, Pulakurthi YS, Aluri S, Aggarwal RK, Ramachandra N, Zhao R, Sahu S, Shastri A, Verma A. Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review. Exp Hematol Oncol. 2023 Jul 8;12(1):60. doi: 10.1186/s40164-023-00422-1. PMID: 37422676; PMCID: PMC10329313.
20. Chai J, Choudhuri J, Wang Q, Fang Y, Shi Y, Kamel J, Shah N, Sica RA, Kornblum N, Konopleva M, Mantzaris I, Shastri A, Gritsman K, Verma A, Goldfinger M, Goel S, Wang Y, Tian X. Acute myeloid leukemias with JAK2/STAT mutations are associated with PD-L1 upregulation. Leuk Lymphoma. 2023 Jul 10:1-11. doi: 10.1080/10428194.2023.2232494. Epub ahead of print. PMID: 37424335.