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Broad Clinical Fellows take a stem cell-based approach to liver disease and bone loss

Broad Clinical Fellows take a stem cell-based approach to liver disease and bone loss

Osteoblasts
"Human osteoblasts in culture" by Vera Malheiro is licensed under CC BY-NC-ND 2.0.

This year’s Broad Clinical Research Fellows are developing stem cell-based approaches for patients of all ages—from two-week-old infants with liver disease, to senior citizens with bone loss following joint replacement surgeries.

Since 2015, the Broad Clinical Research Fellowships have enabled physician-scientists at USC, UCLA and the University of California, San Francisco, to engage in one year of research about stem cell-related approaches to treat injury and disease. The fellowships are potentially renewable for a second year.

Kevin Collon
Kevin Collon

As an Orthopaedic Surgery Resident and Postdoctoral Research Fellow at USC, Kevin Collon will work to demonstrate the safety of a stem cell-based treatment to regenerate bone in patients with fractures that won’t heal and other tough-to-treat conditions. Two previous Broad Clinical Fellows, R. Kiran Alluri and Hyunwoo “Paco” Kang, worked to genetically modify stem cells to send signals to encourage the production of bone, and to surgically implant these stem cells into the injured femurs of rats. In rats receiving the treatment, Collon is testing safety of gene therapy by assessing the local and systemic response to the implantation of genetically modified stem cells in to large bone defects. This is a necessary step before obtaining approval for human clinical trials.

“My career goal is to establish a practice in orthopaedic surgery within an academic teaching institution in which I can perform and incorporate biomechanical, basic science, translational and clinical research,” said Collon. “I am grateful to The Broad Foundation for their support of my current research project, which fits perfectly with my interests and advances my career goals.”

Collon is working under the mentorship two faculty members at the Keck School: Denis Evseenko, who is an Associate Professor of Orthopaedic Surgery, and Stem Cell Biology and Regenerative Medicine; and surgeon-scientist Jay R. Lieberman, who is Chair of the Department of Orthopaedic Surgery.

Johanna Ascher Bartlett
Johanna Ascher Bartlett

A Fellow in Pediatric Gastroenterology, Hepatology and Nutrition at a USC-affiliate, Children’s Hospital Los Angeles (CHLA), Johanna Ascher Bartlett is working to identify biomarkers to guide treatment decisions in children who develop acute liver failure, or ALF. This sudden illness afflicts previously healthy children, prompting liver transplantation in up to 25 percent of patients, and leading to death in up to 15 percent. To help clinicians decide which patients are likely to spontaneously recover, and which ones require interventions, Ascher Bartlett is using patient biopsies to study a subset of the immune cells known as a lymphocytes, which might be associated with more severe cases and provide targets for reducing inflammation and disease progression.

“Being selected as a Broad Clinical Research Fellow is a tremendous honor,” said Ascher Bartlett. “This work will help to prepare me for a lifelong career in academic medicine and research pursuits to further the care of children with liver disease.”

Ascher Bartlett is performing the research under the mentorship of Drs. Juliet Emamaullee and Rohit Kohli, physician-scientists associated with the CHLA Liver Transplant Program and USC.

Allen Zhong
Allen Zhong

A Research Fellow in Developmental Biology and Pediatric Surgery at USC and CHLA, Allen Zhong is also dedicating his efforts to understanding pediatric liver disease. Specifically, he is focusing on the leading cause of pediatric end-stage liver failure and transplantation, which is biliary atresia. To better understand this disease and how to treat it, Zhong is using mice, as well as rudimentary mini-livers called organoids, to study the role of progenitor cells in repairing damage to the ducts that become blocked in BA, often leading to scarring or cirrhosis.

“The Broad Clinical Research Fellowship provides the necessary funding for my training as a clinician-scientist,” said Zhong. “I hope to address clinically relevant questions, specifically in hepatobiliary disease, that will improve patient care and outcomes by utilizing the resources and tools of a basic science laboratory.”

Zhong is performing the research under the mentorship of Kasper Wang, who is a physician-scientist at CHLA, and Kinji Asahina, who is an Associate Professor of Research Pathology at the Keck School of Medicine of USC.

“The Broad Foundation is wise to invest in physician-scientists,” said Andy McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “For a physician-scientist, a patient is not an abstract concept, but a flesh-and-blood human being sitting in an exam room. That’s why physician-scientists are key to translating basic laboratory discoveries into new treatments and cures.”

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