Manoj M Pillai, MBBS
Associate Professor of Medicine (Hematology)Cards
About
Titles
Associate Professor of Medicine (Hematology)
Biography
I am a physician scientist with an interest in the regulation of hematopoiesis in the laboratory. Our group is specifically interested in how RNA mechanisms are important in normal bone marrow physiology and how it is altered in clonal myeloid disorders. Genome-wide transcriptomic techniques are used for these studies.
As a practicing hematologist, I see patients on the inpatient leukemia floor and stem cell transplant floor at the Yale New Haven Hospital.
Appointments
Hematology
Associate Professor on TermPrimaryPathology
Associate Professor on TermSecondary
Other Departments & Organizations
- Center for Biomedical Data Science
- Center for RNA Science and Medicine
- Genomics, Genetics, and Epigenetics
- Hematology
- Internal Medicine
- Molecular Medicine, Pharmacology, and Physiology
- Pathology
- Pillai Lab
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Medicine
- Yale Stem Cell Center
- Yale Ventures
- YCCEH
Education & Training
- Instructor and Research Associate
- Fred Hutchinson Cancer Research Center (2008)
- Fellow
- Fred Hutchinson Cancer Research Center/ University of Washington (2005)
- Resident
- Baylor College of Medicine (2002)
- MBBS
- All India Institute of Medical Sciences (1998)
Research
Overview
1. Role of small RNAs, long non-coding RNAs and RNA binding proteins in marrow microenvironment.
The marrow microenvironment (ME) is comprised of several different subtypes including marrow stromal cells, macrophages, endothelial cells, osteoblasts etc. Various ligands critical to hematopoietic stem and progenitor cells (HSPC) are elaborated by several of these cells types. What is not known is how coordinated expression of these factors is effected across different cell types. We hypothesize that common themes of regulation of gene expression are operant through these cell types. We have implemented several genome-wide techniques including HITS-CLIP (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation) and RNA-Seq to define the role of small RNAs, long non-coding RNAs and RNA-biding proteins in this regulation. Studies are conducted in human stromal cell lines as well as primary human cells from healthy donors.
2. Biology Spliceosome Mutations in Myelodysplastic Syndromes (MDS).
MDS are a heterogeneous group of blood disorders characterized by clonal proliferation of hematopoietic progenitors and low blood counts. Recently, whole genome sequencing has revealed recurring mutations in the RNA-splicing machinery (SF3B1, U2AF1, SRSF2 etc) in up to half the patients with MDS. It is currently unclear how mutations in the highly conserved and ubiquitous splicing machinery can result in the specific phenotype of MDS. We are using a variety of in vivo and in vitro approaches to define the mechanistic basis of these mutations at the molecular, cellular and tissue levels.
3. Musashi Proteins in Aggressive Myeloid Leukemia.
The RNA binding protein Musashi 2 (MSI2) is transcriptionally upregulated in aggressive myeloid leukemia including CML-blast crises and some AML which are resistant to therapies. Although purported to bind to specific sequence motifs in 3’ UTRs of transcripts such as NUMB, unbiased studies have not suggested this to be the mechanism by which MSI2 function in the context of leukemia. Our laboratory is implementing unbiased genome-wide studies including HITS-CLIP to precisely define how MSI2 expression leads to chemoresistance.
Medical Research Interests
Academic Achievements & Community Involvement
Clinical Care
Overview
With an interest in blood cells and how they develop, Manoj J. Pillai, MBBS (a medical degree awarded in several countries outside of the U.S.), always knew he would become a hematologist—a physician who treats blood, bone marrow, and lymph system disorders.
Blood production is a complex process that occurs within specific areas of bone marrow. Every day, healthy individuals produce more than a trillion blood cells. In blood disorders, like leukemia, the process of blood cell development is interrupted.
Dr. Pillai began his training at a time when next-generation sequencing, which allows researchers to quickly determine genetic ordering and structure, was at its start. Since then, Dr. Pillai and his team have integrated these fine-tuned approaches in their work, exploring what leads to oncogenesis—the mutation of regular blood cells.
This information leads to “precision genetic therapies,” which allow doctors to target specific approaches to a patient’s cancer based on their genetic make-up.
Cancer is not a single disease and so each type of cancer will respond differently, but the goal, ultimately is to develop targeted therapies that make toxic treatments such as chemotherapy a thing of the past, Dr. Pillai says.
Dr. Pillai’s research explores different ways blood cells develop abnormally and also specific mutations that can lead to cancers.