Vikram R Paralkar
Vikram R Paralkar
421 Curie Boulevard
Philadelphia, PA 19104
DG Ruparel College, Mumbai, India, 1998.
Seth GS Medical College, Mumbai, India, 2004.
Description of Clinical ExpertiseAcute and Chronic Myeloid Malignancies
Description of Research ExpertiseRESEARCH INTERESTS:
The Paralkar Lab studies how transcription factors and epigenetic proteins regulate the transcriptional landscape of both mRNAs and ribosomal RNAs in normal hematopoiesis, and how dysregulation of these factors leads to acute or chronic myeloid leukemias.
Hematopoiesis, Leukemia, Gene regulation, Ribosome biogenesis, Stem cells
Hematopoiesis is a complex and highly regulated process by which stem cells residing in bone marrow produce a constant stream of blood cells to preserve a functional hematopoietic system throughout the duration of a human lifespan. Mutations in epigenetic regulators, transcription factors, splicing proteins and tumor suppressors can derange the normal course of hematopoiesis, and lead to clonal expansion and leukemia. Understanding the epigenetic and transcriptional consequences of these mutations is essential for understand both normal hematopoietic homeostasis as well as hematopoietic malignancies. Several key hematopoietic factors and leukemia-mutated proteins also regulate the transcription of ribosomal RNA, and dysfunctional ribosome biogenesis can cause bone marrow failure or malignancy.
In the Paralkar Lab, we apply state-of-the art molecular biology techniques to in vitro and in vivo models of hematopoiesis and leukemia to study normal blood development and the mechanisms of leukemogenesis. Our goal is to understand how fundamental mechanisms in epigenetic and transcriptional regulation are responsible for maintaining normal hematopoietic stem cell function and myeloid differentiation, and suppress myeloid leukemia.
1) Dissecting how hematopoietic cell-type-specific transcription factors bind to ribosomal DNA genes and regulate transcription of ribosomal RNA.
2) Dissecting the role of the chromatin binding protein PHF6 in represses normal hematopoietic stem cell self-renewal, and studying how its mutation promotes leukemia stem cell self-renewal.
Sapana Jalnapurkar, PhD - Postdoctoral fellow
Charles Aruljothi, PhD - Postdoctoral fellow
Aishwarya Pawar - Graduate Student
Subin George - Bioinformatician
Erin Gray - Research Specialist
Jason Grana - Research Specialist
Aleena Alex - Undergraduate Student
Selected PublicationsAntony C, George SS, Blum J, Somers P, Thorsheim CL, Wu-Corts DJ, Ai Y, Gao L, Lv K, Tremblay MG, Moss T, Tan K, Wilusz JE, Ganley ARD, Pimkin M, Paralkar VR: Control of ribosomal RNA synthesis by hematopoietic transcription factors. Molecular Cell Oct 2022.
Lv K, Gong C, Antony C, Han X, Ren J, Donaghy R, Cheng Y, Pellegrino S, Warren AJ, Paralkar VR, Tong W: HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis. Cell Stem Cell 28: 1-16, Jul 2021.
Xu P, Palmer LE, Lechauve C, Zhao G, Yao Y, Luan J, Vourekas A, Tan H, Peng J, Scheutz JD, Mourelatos Z, Wu G, Weiss MJ, Paralkar VR: Regulation of gene expression by miR-144/451 during mouse erythropoiesis. Blood 133(23): 2518-2528, Jun 2019.
Traxler EA, Thom CS, Yao Y, Paralkar V, Weiss MJ: Non-specific inhibition of erythropoiesis by short hairpin RNAs. Blood 131(24): 2733-2736, Jun 2018.
Paralkar VR, Taborda CC, Huang P, Yao Y, Kossenkov AV, Prasad R, Luan J, Davies JO, Hughes JR, Hardison RC, Blobel GA, Weiss MJ: Unlinking an lncRNA from Its Associated cis Element. Molecular Cell 62(1): 104-10, Apr 2016.
Paralkar VR, Mishra T, Luan J, Yao Y, Kossenkov AV, Anderson SM, Dunagin M, Pimkin M, Gore M, Sun D, Konuthula N, Raj A, An X, Mohandas N, Bodine DM, Hardison RC, Weiss MJ: Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development. Blood 123(12): 1927-37, Mar 2014.