Originally published by Lindsey Morris for the AU Campus Insider at https://insider.augusta.edu/georgia-cancer-center-researcher-rewarded-2-8-million-nci-nih-grant-for-breast-cancer-research/

The National Cancer Institute, NCI, is the federal government’s principal agency for cancer research and training. This funding agency fellows an extremely rigorous and highly competitive process to select promising cancer research proposals for funding across the nation. They are currently the largest cancer research funding provider in the world and have awarded one of our own with a prestigious grant.

“We are honored and humbled to be trusted by the NCI to further develop this project that has been central to our lab for many years. Without this grant, we can’t take this promising project to the next level,” says Chadli Ahmed, PhD.

Ahmed is an associate professor of Biochemistry, Molecular Biology, and Graduate Studies, at the Medical College of Georgia and the Georgia Cancer Center. His lab focuses on understanding the biology of cancer, specifically breast cancer, and developing novel drugs against triple-negative breast cancer (TNBC). TNBC is a highly aggressive cancer and a challenge to treat as it does not express estrogen or progesterone receptors, nor does it make a lot of the HER2 protein, which renders treatments that target these proteins useless. Thus, there is an urgent need to identify new therapeutic targets and develop new therapies against TNBC.

Cancer cells are mutated cells that have a lot of misstructured and malfunctioning proteins. These cells are normally recognized by our defense mechanism called the immune system and destroyed, just as viruses and bacteria are. However, over time, few of these cells escape this immune reaction by developing suppressive immune mechanisms that allow them to grow without interference from the immune system. Cancer cells do this by exposing a few proteins on their surface that suppress the ability of T-cells, the ‘soldiers’ of the immune system, to kill cancer cells. This allows cancer cells to multiply to form tumors and spread throughout the body, a process called metastasis.

The grant awarded for Chadli’s research focuses on a specific protein, UNC45A, that can be used as a promising novel immunotherapeutic target. He and his lab team hypothesize that by inhibiting this protein which is the act of blocking growth for cancer cells and activates the immune system to eliminate tumors. They also believe that combining this inhibition with radiation therapy will efficiently reduce the TNBC burden.

“We believe this protein is an exciting alternative target to develop more efficient treatment of breast cancer.”

Ahmed started this research nearly 22 years ago when he was a postdoctoral fellow in David Toft’s lab at the Mayo Clinic in Rochester, MN. Over the years he has dissected the biochemical and cell biological functions of this protein. More recently he has genetically engineered sophisticated tools that allowed testing the impact of inhibiting this protein in mice. The data used to support this application have established the key role of UNC45A in promoting tumor growth and how inhibiting this protein eliminates tumors through the reactivation of the immune system to recognize them.

The next step for him and his team is to identify small molecules or antibodies that will assist them in inhibiting the protein in humans. Motivated fellows in Chadli’s lab are working hard to establish a platform for high-throughput screening of compound inhibitors of UNC45A and other molecular chaperones to treat TNBC.

In the next five to ten years, he hopes to have the project in the clinical trials stage.“The impact of this work on human health will be, we hope and believe, very significant.”