Dr Charles Chan – If I could turn back time

Dr Charles Chan – If I could turn back time

Dr Charles Chan is an Assistant Professor at Stanford in the Department of Surgery, Division of Plastic and Reconstructive Surgery, with co- appointments in the Immunology Program and the Stem Cell Institute. Dr Chan has always been fascinated by the process of aging both as a biological phenomenon as well as its association with highly prevalent diseases such as cancer and cardiovascular disorders, both of which are more prevalent in older populations. After the now famous cloning of Dolly the sheep, Dr Chan realized that cloning could have therapeutic applications and could therefore mean molecular rejuvenation, essentially reversing aging, might be in fact be feasible. Impressively during his post-doctoral studies Dr Chan identified both mouse and human stem cells.

What’s the Difference?

Stem cells are cells that are capable of differentiating into numerous different types of cells, making them a great potential resource to address aging. This young researcher is studying skeletal aging from the perspective of its regenerative stem cells. Slight differences between young skeletal stem cells (SSCs) compared to older SSCs could accumulate, and the differences could contribute to a progressive decline in bone tissue integrity and a reduction in regenerative potential. Previous research undertaken by Dr Chan and his team showed that disease, in this case diabetes mellitus, led to characteristics in bones similar to those seen in aging, such as osteoporosis and insufficient bone healing.

The Hedgehog signaling pathway is responsible for the transmission of information to embryonic cells required for proper cell differentiation. In other words, hedgehog signalling instructs our embryonic cells on how to specialise, producing the different types of cells needed to perform different functions. This signalling pathway is also important for adult stem cell differentiation. It was determined that a deficiency in this pathway signal was responsible for the SSC frequency and activity being diminished as seen in the diabetic bone. Excitingly extrinsic delivery of Indian hedgehog (a cell signalling protein involved in the pathway) restored the signalling defect ensuring SSC mediated bone formation during bone repair could proceed. Stem cells are the source for new cells required to replace those lost to injury or disease. Identifying pathways and molecules necessary for specific stimulation of specialised cells will be key in unlocking the treatment potential of these starter cells.

Stemming the Tide of OA Destruction

A stem cell niche refers to a microenvironment, with a specific anatomical location, where stem cells are found. Factors in these microenvironments interact with the stem cells helping to regulate its differentiation into a required specialised cell.  Dr Chan has been working on finding novel approaches to transplant stem cell niche factors into sites of injury to stimulate regeneration in a specific area requiring a specific type of cell. Dr Chan has had success in using soluble protein factors to drive differentiation of SSCs towards the formation of bone, cartilage or stromal cells. These and other findings by the group offer significant hope for treatment of a number of conditions, particularly those that mimic aging and reduce regeneration of cells and tissues. What this boils down to is creating environments which force starter cells to become the cells we need. Playing classical music to your child may increase the likelihood of your child becoming an accomplished pianist. In the same way if you put certain factors into the stem cell environment you could increase the likelihood of it differentiating into the desired cell type.  For example, in patients with arthritis, in which bone degenerates it can be immensely helpful to drive SSCs to form new bone and cartilage to replace that which has been damaged or lost. Building on these foundations, recent data suggests that it is in fact possible to reverse cartilage degeneration by activating SSCs.  By stimulating the cells surgically as well as providing essential niche factors, the resting stem cells can be directed to differentiate into cartilage.

Dr Chan is now applying state of the art techniques to characterize the changes at a molecular level that tissue specific stem cells undergo with age, in hopes of finding new ways to rejuvenate tissues by revitalizing and directing their stem cells. This could offer innumerable new ways to treat diseases in which aging plays a significant role.

Building on Promise

On becoming an ANRF scholar Dr Chan had the following to say, “I am deeply grateful for the generous support of the American Federation for Aging Research and the Arthritis National Research Foundation, in granting me this prestigious award. It will greatly enable our young group’s efforts to build on our very promising studies on regenerating cartilage to reverse osteoarthritis. At the same time, it gives me a critical boost at an early stage as an assistant professor and scientist dedicated to the understanding and hopefully reversal of stem cell aging.”

Despite his extraordinary achievements’ Dr Chan has remained an incredibly humble researcher. At the end of his interview with ANRF researcher communication manager he took pains to thank those he felt had contributed greatly to his academic and research journey. “I also wish to thank the wonderful teachers who gave me so much love, and encouragement during my formative years including Katherine McKinney, Cheryl Sutherland, Duane Nichols, Michelle Poirier, Hsiao Ping Moore, Mark Bennett, Ashraf Imam, Irv Weissman, and Michael Longaker. I also want to thank my amazing trainees; Matthew P Murphy, Lauren Kopeke, and Tom Ambrosi in my group for their phenomenal contributions to this project and for allowing me to join them on their expeditions to find new Shangri La’s and Fountain of Youths. Last but not least I wish to thank my family.” At ANRF collaboration is key in the fight against autoimmune conditions and we are gratified to be play a small role in the efforts by researchers such as Dr Chan. We wish him the best in his time as an ANRF scholar and look forward to seeing the inroads he will surely make in achieving his objectives.

 


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ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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