Dr. Priya Kishnani is the C.L. and Su Chen Professor of Pediatrics and the Chief of the Division of Medical Genetics at Duke University. She also holds the position of Professor in the Department of Molecular Genetics and Microbiology and is Medical Director of the YT and Alice Chen Pediatrics Genetics and Genomics Center.
Dr. Rebecca Koch is an Assistant Professor in the Division of Medical Genetics at Duke University and registered dietitian. She currently oversees the Glycogen Storage Disease (GSD) translational research program for Dr. Kishnani which focuses on defining the natural history, pathophysiology, and factors related to treatments for GSDs.
In 2023, Dr. Kishnani and Dr. Koch received a Million Dollar Bike Ride grant titled “Deep Tissue and Cellular Phenotyping of APBD: A Bench to Bedside Approach.” Their aim is to increase the knowledge and understanding of the specific cells and tissues involved in APBD, as well as assess how the pathology changes over the course of the disease.
We interviewed Dr. Kishnani and Dr. Koch recently to give you a chance to get to know them and the innovative APBD research being done at Duke University Medical Center.
Priya Kishnani, MD, MBBS and Rebecca Koch, RDN, LDN, PhD at Duke University Medical Center
Q: What inspired you to pursue this field of research?
Dr. Koch: My doctorate training focused on the impact of genetics on metabolic pathways. Then, during my clinical training, I counseled patients with inherited metabolic disorders and that’s when it all “clicked” – I knew this is the field I wanted to continue working in. As a researcher of glycogen storage diseases and other rare inborn errors of metabolism, I have the opportunity to work with families, physicians, and scientists from all over the world. Hearing that our work has had an impact on patient lives is so rewarding and encouraging, and I cannot imagine working in any other field.
Dr. Kishnani: The Duke Health Rare Disease Center has a long history of research in GSD IV to improve patient management. Back in the 1990s, our team published on four cases of GSD IV with “non-progressive” hepatic GSD IV. Since then, we have learned that the disease is not “non-progressive,” but rather the liver disease may be attenuated. We have also learned that there are individuals with GSD IV who have hepatic disease in childhood but can develop APBD in adulthood. Given that there are many phenotypes of GSD IV, including the adult-onset form APBD, we have continued to research more into how the disease evolves through our GSD IV/APBD natural history study, analyzing patient samples in our biorepository, and characterizing the Gbe1ys/ys mouse model.
Interested in sharing your APBD experiences via the “GSD IV, including APBD, Natural History Study?”
Contact Dr. Rebecca Koch at rebecca.koch@duke.edu or +1-919-681-8823.
Q: Your work focuses on understanding tissue and cellular involvement in APBD and correlating polyglucosan levels with serum biomarkers. Why is this area critical?
Dr. Koch: Designing effective and efficient therapies for GSD IV relies on our comprehensive understanding of (1) the model we are using (in this case, the mouse model), and (2) how this model compares to the patient. Our project is focused on delineating what cells are involved, where polyglucosan is aggregating, and to what degree polyglucosan is accumulating. This work is at the tissue level and requires relatively large samples of tissue. Yet, since obtaining tissue biopsies is invasive, can be painful, and in some cases not possible (such as for the brain), less invasive markers of disease are ideal for evaluation of disease. By correlating our tissue findings with biomarkers in blood, urine, and other non-invasive markers such as imaging modalities, we will improve our understanding of the role of these biomarkers in clinical disease and hence impact during clinical trials and patient management.
Some of the members of the Kishnani-Koch Lab
From left to right: Priya Kishnani, MD, MBBS; Jeong-A Lim; Neha Regmi, MBBS, MD; Rebecca Koch, PhD, RDN, LDN; Garima Shrivastava, PhD; Su Jin Choi, PhD; Fiona Weaver, MS.
Q: How did you approach designing this project?
Dr. Kishnani: Dr. Koch and I are clinical and translational researchers, so we wanted to design a project that incorporates both patient and animal model samples to ensure our findings accelerate therapy development. We have a repository of patient samples along with a natural history study, and we also maintain a colony of the GSD IV mouse model (Gbe1ys/ys). When we designed this project, we leveraged the expertise of neuropathologist Dr. Karra Jones and gastro-intestinal/liver pathologist Dr. Will Jeck to evaluate several tissues from both patients and the mouse model.
Q: How is the research progressing so far?
Dr. Koch: We have completed the analysis of mouse tissues and are in the process of comparing these findings to those from patient autopsies. When we were originally awarded this funding, we had samples from one autopsy. Now, because of the seminal contributions from the families, we have tissue from three patient autopsies. This research would not be possible if it were not for the families of these patients deciding to give the ultimate gift to our research. We expect our analysis to be completed in 2025.
Q: Your research has important implications for clinical trials in APBD. Can you tell us more about this?
Dr. Kishnani: We expect that pilot data generated from this study will provide specific cells to target and will better inform future therapy approaches. We hope that this will allow for more effective clinicals trials.
Thank you, Dr. Kishnani and Dr. Koch. We wish you much success on behalf of our community!
