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Massey researcher studies protein found in cancer cells and platelets to inform the treatment of chronic inflammatory diseases

"Eddie" Wook-Jin Chae, Ph.D.

VCU Massey Cancer Center researcher “Eddie” Wook-Jin Chae, Ph.D., studies a protein found in blood cells that inhibits tissue injury repair in hopes of informing the development of a novel antibody for the treatment of chronic inflammatory diseases such as cancer and asthma.

Chae joined Massey as a member of the Cancer Cell Signaling research program in 2019. He is also an assistant professor of microbiology and immunology at the VCU School of Medicine.

Chae primarily studies the fundamental mechanisms by which the protein Dickkopf1 (DKK1) dysregulates immune cell response in inflammatory diseases including cancer.

The WNT signaling pathway is vital for the development and regeneration of most organs in the body, and dysregulation of the WNT pathway leads to fibrosis and cancer.

DKK1 is an inhibitor of the WNT pathway, and was prevalent in models of cancer, asthma and other chronic inflammatory diseases. Further investigation by researchers including Chae revealed that DKK1 is expressed by cancer cells, platelets and other immune cells such as regulatory T cells. Platelets have primarily been associated with the function of blood clotting; however, Chae and others showed that platelets may play a significant role in modulating immune response.

In the face of environmental challenges such as pathogens, allergens and carcinogens (among others), the immune system is activated to repair damaged tissue and remove inflammation. Chae found that DKK1 is an antagonistic factor to this process by delaying tissue repair and dysregulating the facilitation of proper immune response.

“If you have a lot of DKK1 in the tissue, or the blood, the wound healing process is being delayed, which is a perfect condition for chronic inflammation,” Chae said. “Cancer is known as a disease or wound that does not heal — it’s chronic. It is not surprising that DKK1 is highly expressed in tumor tissues or that it is found in the blood at high levels.”

Chae said that it is surprising that there has been such a limited number of studies to understand DKK1 and explore it as a novel strategy to treat cancer and other chronic inflammatory diseases since it was identified almost two decades ago.

“We believe that there are many opportunities to understand cancer from different perspectives and provide new insights for cancer immunotherapy,” he said.

Chae argues that there is sufficient literature demonstrating the expression of DKK1 in all major cancer types (including lung, pancreatic, blood, breast and ovarian cancers) to support the development of a novel antibody for disease treatment. A DKK1 antibody was previously developed by a therapeutics company, but only for application in bone diseases such as multiple myeloma or osteoporosis.

“I’m proposing the use of a DKK1 antibody in combination with a chemotherapeutic regimen or immune checkpoint inhibitor to broaden the scope of cancer patients who can be treated,” said Chae, who holds a patent for the use of a DKK1 inhibitor in chronic inflammation.

He added that it’s relatively simple to identify the level of DKK1 in a person’s blood through a liquid biopsy to determine whether the antibody is a strategic treatment method for that patient. Chae said there are many more WNT ligands and antagonists that have not been researched yet, and more research opportunities will come very soon.

Chae has been published in more than 25 peer-reviewed journal publications including  Immunity, Proceedings of the National Academy of Sciences, Differentiation, and Trends in Immunology, among others.

He grew up in Seoul, South Korea, and earned a Ph.D. in immunology from Yonsei University, just after he finished a overseas scholarship program at Yale during his Ph.D. training. His early academic career focused on T-cell activation signaling mechanisms. Chae completed a post-doctoral fellowship in immunobiology at Yale University where his research primarily centered around models of inflammation in the gut including colon cancer. He worked as a research scientist at Yale for five years before joining VCU, broadening his research into various aspects of DKK1 as an immunomodulator.

Chae cited the friendly, cooperative and resourceful environment as a major reason for coming to VCU.

“Multidisciplinary expertise is required to further advance my research, and I was very impressed by how open Massey research members are to new investigators and how many resources there are available at Massey,” he said. “I am looking forward to being part of exciting research programs at Massey.”

Written by: Blake Belden

Posted on: July 10, 2019