Shastri Lab

At the Shastri Translational Research Lab, we are committed to advancing the understanding and treatment of hematopoietic diseases, with a particular focus on myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Our research encompasses several interrelated domains.

Hematopoietic Stem and Progenitor Cell (HSPC) Targeting Therapeutics

Recent research suggests that myeloid malignancies originate from leukemic stem cells, and their progression is driven by the persistence and survival of these cells. We are developing innovative therapies targeting HSPCs in myeloid malignancies, focusing on targeting Signal Transduction and Activator of Transcription 3 (STAT3) pathway. STAT3 is a key regulator that is overexpressed in hematological malignancies and is associated with reduced overall survival. In our lab, we have targeted STAT3 using several novel agents, including antisense oligonucleotides and degraders, in leukemic cell lines, generating promising preclinical data. We aim to translate these findings into early phase clinical trials. 

Interactions of STAT3 in HSPCs 

We are investigating how STAT3 interacts with apoptosis inhibitors such as BCL2, MCL1in HSPCs, as well as how these interactions are influenced by inflammatory environment in the bone marrow niche. This work could reveal novel therapeutic strategies to overcome resistance in myeloid malignancies. 

Aging-Related Clonal Hematopoiesis (CH) 

In collaboration with Dr. Millman and her team, we are studying a longevity cohort enriched for centenarians. This research aims to uncover how centenarians resist age-related diseases, such as cancer, cardiovascular disease, and Alzheimer’s. Specifically, we are examining the frequency and type of CH mutations in these individuals and investigating whether longevity provides protection against harmful CH mutations. 

The Effect of Air Quality and Other Environmental Health Hazards on Myeloid Malignancies 

We analyze large datasets to understand differences in the incidence, treatment, and outcomes of myeloid malignancies. By identifying social, genetic, and environmental factors, specifically differences in air quality, we aim to develop strategies to effect policy change and improve cancer patient outcomes across the world.

Shastri A, Daver NG, Hayes TG. Primary Gastric Chorioadenocarcinoma: A case report and review of literature. Rare Tumors. 2011 Apr, PMID: 21769318
 

Cooperman,N; Shastri JS; Shastri, A; Schoenbaum, E; HIV Prevalence, Risk Behavior, Knowledge and Beliefs among Women Seeking Care at a Sexually Transmitted Infection Clinic in Mumbai, India. Health Care Women Int. 2013 Mar 4, PMID: 23659311
 

Daver N, Shastri A, Kadia T, Quintas-Cardama A, Jabbour E, Konopleva M, O'Brien S, Pierce S, Zhou L, Cortes J, Kantarjian H, Verstovsek S. Modest activity of pomalidomide in patients with myelofibrosis and significant anemia. Leukemia Research. 2013 Jul 24, PMID: 23890523
 

Murthy SB, Karanth S, Shah S, Shastri A, Venkatasubba Rao CP, Bershad E, Suarez JI. Thrombolysis for Acute Ischemic Stroke in Patients with Cancer: A Population Study.
Stroke. 2013 Dec; PMID: 2406571
 

Murthy SB, Moradiya Y, Shah S, Shastri A, Bershad E, Suarez JI. In-hospital Outcomes of Thrombolysis for Acute Ischemic Stroke in Patients with Primary Brain Tumors.
Journal of Clinical Neuroscience. 2014. PMID: 25564270
 

Shusterman M, Bloomgarden NA, Sotardi ST, Shastri A. Tumor Lysis Syndrome in an Unusual Metastatic Pancreatic Neuroendocrine Tumor with Ectopic ACTH Secretion.
J Gastrointest Cancer. 2015 Aug 14, PMID: 26271662
 

Daver N,* Shastri A,* Kadia T, Quintas-Cardama A, Pemmaraju N, Jabbour E, Konopleva M, O’Brien S, Pierce S, Cortes J, Kantarjan H, Verstovsek S. Phase II study of pomalidomide in combination with prednisone in patients with myelofibrosis and significant anemia.
Leukemia Research 2014 Jul, PMID: 25047979 * Equally Contributed