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A montage of different images of cells, each of which was collected from a 384 well plate using high throughput imaging. Cells were transfected with siRNA to knock down one gene at a time and analyzed using elliptical Fourier analysis to quantify nuclear contour irregularities. DNA is blue, F-actin in red, and lamin A/C in green. | Image: Dr. Tanmay Lele

A new faculty member in the Department of Biomedical Engineering at Texas A&M University recently received a multi-million dollar grant to support groundbreaking cancer research.

In May, Dr. Tanmay Lele received a $5 million Recruitment of Established Investigators grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to further knowledge about cancer and how it progresses. 

Lele’s research focuses on mechanobiology — the mechanical aspects of biology — where he works to understand how cells sense external mechanical forces as well as how they generate mechanical forces, and how these mechanical forces impact cell function.

In cancer, both cellular mechanical forces and the mechanical properties of resisting cellular structures go awry. These errors cause abnormalities in cell structure. A particularly striking feature of cancer cells is the highly irregular and/or distended shape of the nucleus.

“The nuclei in normal tissue have smooth surfaces, but over time the surfaces of cancer nuclei become irregular in shape,” Lele said. “Now, why? Nobody really knows. We’re still at the tip of the iceberg at trying to figure this problem out. But nuclear abnormalities are ubiquitous and occur in all kinds of cancers — breast, prostate and lung cancers.”

Pathologists study biopsies and note abnormalities in the shape of the cell and its nucleus to grade the severity of cancer. Lele and his team are computerizing the analysis of nuclear shapes to research the cause of abnormal cancer structures.

Using photos of nuclei and cells in human tissue taken by a pathologist, Lele’s team has developed a computational algorithm to measure the degree of irregularity in the nucleus. With the algorithm, the team can run statistical analyses of the abnormalities and search for correlations between the extent of the irregularity, changes to genetic or molecular signatures in tumors and, ultimately, patient outcomes.

Lele’s research aims to help the medical community develop new knowledge of human cancers and how they progress, to better diagnose and manage cancers. Understanding the mechanisms behind the abnormalities can help develop therapies to better treat cancers by targeting the nucleus. 

“Like any other basic field, we are trying to make discoveries with the hope that they will have long-term impacts on human health,” Lele said.

Lele will have two laboratories, one in College Station and one in the Texas A&M Health Science Center’s Institute of Biosciences & Technology in Houston. The cancer grant from CPRIT is a collaborative effort with Dr. Michael Mancini and Dr. Fabio Stossi from the Baylor College of Medicine. He said he is looking forward to collaborating with researchers in both College Station and Houston.

Lele received his doctoral degree in chemical engineering from Purdue University. Before coming to Texas A&M, he served as the Charles A. Stokes Professor of Chemical Engineering at the University of Florida. At Texas A&M, in addition to being in biomedical engineering, he will be a joint faculty member in the Artie McFerrin Department of Chemical Engineering. 

“All my career has been spent in chemical engineering departments, but my research is also now in the biomedical space,” Lele said. “The move to Texas A&M was an opportunity for me to also be part of a different culture, if you will, of research. Being in the biomedical engineering department, in addition to the chemical engineering department, brings new opportunities to collaborate with researchers who have closely shared research interests.”