Role of Adhesive Signals in Acute Myeloid Leukemia

Speaker Name: 
Jeevisha Bajaj
Speaker Title: 
Assistant Project Scientist
Speaker Organization: 
Department of Pharmacology, UC San Diego
Start Time: 
Thursday, February 14, 2019 - 12:00pm
End Time: 
Thursday, February 14, 2019 - 1:00pm
Location: 
Biomed 200
Organizer: 
Chris Vollmers

Abstract:  

Acute Myelogenous Leukemia (AML) is a poorly differentiated aggressive myeloid cancer, associated with significantly poor survival in both children and adults. There is thus a critical need to better understand mechanisms that drive disease progression and to find novel therapeutic targets. While intrinsic signals promoting AML progression are well described, little is known about how interactions with the microenvironment can control cancer growth. Dr. Bajaj has shown that loss of adhesive signaling, driven by the cell surface proteins Tetraspanin 3 (Tspan3) and CD98, has a significant impact on growth of aggressive AML cells in vivo. She identified Tspan3 as a key new signal required for SDF1-dependent localization of leukemic cells in their niche. Her experiments with CD98, an integrin-binding protein, define a novel role for integrin-mediated adhesion to endothelial cells in sustaining leukemic stem cells (LSCs); and, real time in vivo imaging linking CD98 to long-term interactions of leukemic cells with blood vessels is the first evidence of such interactions occurring in vivo. Importantly, her work showing that a therapeutic-grade CD98 antibody can block the growth of primary patient derived AML cells in vivo led to Phase I clinical trials. Collectively, these studies indicate that inhibiting adhesive signaling may be of therapeutic value in both adult and pediatric AML.

To identify novel microenvironment driven signals, she has recently carried out an in vivo genome-wide CRISPR/Cas9 screen in LSCs and identified genes critical for the growth of the population that drives cancer progression. She now proposes to use this work as a basis to characterize the functional contribution of candidate cell surface molecules, which can integrate signals from the environment, on the growth and progression of myeloid malignancies. These studies will contribute to the design of novel therapies targeting interactions supporting growth and survival of LSCs in their niche.

Bio:

Dr. Jeevisha Bajaj obtained her Ph.D. degree in Cancer Biology in 2012 from the National Center for Biological Sciences, a premier research institute in India. During her Ph.D. she identified and characterized the cancer stem cell population in cervical cancers and defined the role of Notch signaling in sustaining these cells. As a Posdoctoral Fellow and an Assistant Project Scientist in Tannishtha Reya’s lab at the University of California, San Diego she studies the role of adhesive interactions of cancer cells with their environment on the growth and progression of Acute Myelogenous Leukemia (AML).