Award

Dagar dissects a prostate cancer driver

Meet a JBC/Tabor award winner
Alyson Smith
Feb. 8, 2020

Many cancer treatments block hormones that drive tumor cell division and metastasis. These therapies only shrink tumors temporarily, however, as cancer cells can use alternative signaling pathways to reduce their hormone dependence. Drugs that target these pathways may halt tumor growth and extend patient survival.

The 2020 JBC Herbert Tabor Early Career Investigator Award winners will present their work at the 2021 ASBMB Annual Meeting, 1:45–3 p.m., Tuesday, April 27.

Find out about registering for the annual meeting here.

Manisha Dagar has uncovered the details of a signaling pathway that drives advanced prostate cancer.

Dagar-Manisha-300x300.jpg
Manisha Dagar

Dagar has always been interested in science, especially biology. Her mother encouraged her to pursue higher education and a research career. She earned an undergraduate degree in biotechnology, and a summer internship at the National Centre for Disease Control in New Delhi gave her the lab experience she needed to pursue a Ph.D. at Amity Institute of Biotechnology, Amity University in Haryana, India.

At Amity University, Dagar decided to study the molecular biology of cancer. She joined Gargi Bagchi’s lab, where she studies androgens, the male sex hormones, in prostate cancer. Previous research revealed that protein kinase A, which phosphorylates proteins to change their functions, can activate androgen signaling in the absence of hormones. Dagar and colleagues in the lab discovered how this aberrant activity contributes to prostate cancer progression.

Dagar studied protein kinase A function in a cell line derived from a prostate cancer patient. After optimizing protocols to measure protein levels in these cells, Dagar could track how blocking protein kinase A phosphorylation activity changed androgen signaling. Her work has revealed new drug targets that could treat advanced prostate cancer.

Dagar successfully defended her Ph.D. thesis in January. She hopes to pursue postdoctoral research studying cell signaling. Outside the lab, she enjoys reading and traveling.

Targeting molecular chaperones to stop prostate cancer

Testosterone and related androgen hormones act through the androgen receptor, which is stabilized in the cytoplasm by the molecular chaperone HSP90. When the receptor binds an androgen, it releases HSP90 and enters the nucleus to regulate gene expression. Androgens thus direct the development and maintenance of the prostate gland but also drive prostate cancer.

Manisha Dagar and her colleagues knocked down protein kinase A to learn how this enzyme affects androgen receptor nuclear entry. They discovered that protein kinase A phosphorylates HSP90, causing it to release the androgen receptor. The receptor then binds HSP27, a different molecular chaperone, which helps it enter the nucleus. Once in the nucleus, the receptor can bind certain DNA regions to turn on genes.

Blocking protein kinase A activity blocked testosterone-induced HSP90 phosphorylation, androgen receptor-HSP90 dissociation, androgen receptor-HSP27 binding, androgen receptor nuclear entry, changes in gene expression and increase in proliferation of prostate cancer cells.

“By targeting HSP90 phosphorylation by protein kinase A, androgen signaling in prostate cancer cells can be blocked,” Dagar said. “This can be used as a therapeutic target for treatment of prostate cancer.”

As first author on the paper reporting this research, Dagar received a 2020 Journal of Biological Chemistry/Herbert Tabor Early Career Investigator Award.

Dagar and her colleagues continue to search for ways to block prostate cancer cell proliferation, including in patients that express hormone-independent variants of the androgen receptor.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Alyson Smith

Alyson Smith is a recent Ph.D. graduate in cell biology from Scripps Research in La Jolla, California. She now works as a scientific writer for Vala Sciences Inc.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in People

People highlights or most popular articles

‘With advances in mass spectrometry, we can explore terra incognita’
Interview

‘With advances in mass spectrometry, we can explore terra incognita’

Sept. 29, 2022

A conversation with Molecular & Cellular Proteomics associate editor Albert Heck, a researcher at Utrecht University.

In memoriam: Clark Bublitz
In Memoriam

In memoriam: Clark Bublitz

Sept. 26, 2022

He was a metabolic enzymologist and a member of the American Society for Biochemistry and Molecular Biology since 1963.

Understanding protein dynamics to design better drugs
Research Spotlight

Understanding protein dynamics to design better drugs

Sept. 21, 2022

C. Denise Okafor is an assistant professor of biochemistry and molecular biology at Penn State and recipient of an NSF CAREER award.

Computation is the new experiment
Annual Meeting

Computation is the new experiment

Sept. 20, 2022

This symposium, Artificial Intelligence and Machine Learning in Structural Biology, Drug Design and Systems Biology. will be part of #DiscoverBMB 2023 in March.

Kuriyan to take over as dean;  Johnson wins Pew scholarship
Member News

Kuriyan to take over as dean; Johnson wins Pew scholarship

Sept. 19, 2022

Awards, promotions, milestones and more. Find out what's going on in the lives of ASBMB members.

'Keep developing your expertise'
Interview

'Keep developing your expertise'

Sept. 16, 2022

Anand Balakrishnan is a biochemist at Enanta Pharmaceuticals. He leads a team that has worked on respiratory syncytial virus, SARS-CoV-2 and hepatitis B virus.