01/13/2020
2020 Caregiver Catalyst Awards Boost GMI and CPGH Research
Jennifer Hockings, PharmD, PhD, BCPS, Center for Personalized Genetic Healthcare, Pharmacy, and Asha Kallianpur, MD, MPH, Genomic Medicine Institute, were among the 20 caregivers selected to receive a January 2020 Caregiver Catalyst Grant.
Studying the association between pharmacogenomic genes and opioid use
Dr. Hockings will co-lead with Steve Insler, DO, Anesthesiology Institute, a multidisciplinary research team that will investigate if certain pharmacogenomic genes affect how postoperative patients respond to pain medications.
Pharmacogenomics, which is the study of how an individual’s genetic makeup affects their response to medications, is harnessed to understand why some patients metabolize medications differently than others and can identify if certain medications should be avoided or prescribed at a different dose.
Following surgery, patients routinely take prescribed opioids to manage short-term pain. However, this practice significantly increases some individuals’ risk of long-term use, which may be due, in part, to certain pharmacogenomic genes (e.g., CYP2D6) that influence how quickly or effectively the opioids work.
Drs. Hockings and Insler are seeking to identify the patients who, based on their genetic makeup, may not experience effective pain relief using opioids, thus making them more susceptible to long-term use. Utilizing pharmacogenomic testing and data on opioid and other pain medication use in postoperative patients, they will study the association between pharmacogenomics and pain management following surgery. Their findings will provide insight into how postoperative pain management can be tailored for individual patients, which may help limit the risk of long-term opioid use.
This project is entitled “Precision Medicine: Effect of Pharmacogenomic Genes on Post-Operative Pain Control.” Ben Hohlfelder, PharmD, Pharmacy; Chen Liang, PhD, Quantitative Health Sciences; and Jennifer Owens, Information Technology Division, are members of the research team.
Finding biomarkers of aging-related diseases in patients with HIV
Dr. Kallianpur will lead a multidisciplinary study to identify potential drivers of accelerated aging in people with HIV (PWH), including chronic kidney disease (CKD) and cognitive impairment.
Despite increased life expectancy on antiviral therapy, PWH inexplicably experience an unusually high burden of aging-related diseases, with major adverse impact on functional status and quality of life. CKD and cognitive impairment are two diseases of aging that often co-occur in PWH, causing increased risk of frailty and death.
Dr. Kallianpur’s team aims to identify non-invasive biomarkers of CKD and cognitive decline, which are urgently needed to stratify risk and inform new therapies. Her laboratory discovered that higher levels of certain iron-regulatory proteins in the central nervous system predict better cognitive performance in PWH over 42 months of follow-up in populations including high-risk genetic subgroups. Preliminary data also link the same proteins to known pathways of injury, suggesting that an HIV-related imbalance of key iron-related proteins may drive up injury molecules in brain, kidney, and other tissues.
In this project, iron-related and renal-injury biomarkers will be quantified in PWH from a large HIV cohort and associated with development of CKD, cognitive impairment, and frailty over follow-up. Study findings could highlight a novel aging-related pathway, suggest new therapeutic interventions, and attract external funding for a clinical trial. Most importantly, this study could confirm the value of low-cost, noninvasive and widely applicable biomarkers of early renal injury and cognitive decline, improving care for PWH in diverse clinical settings.
This project, entitled, “Shared Mechanisms and Markers of Renal Injury and Cognitive Decline in People with HIV,” includes the following research team members: John Sedor, MD, Nephrology and Hypertension; Robert Kalayjian, Chief, Infectious Diseases, MetroHealth Medical Center; William Bush, Case Western Reserve University Department of Population and Quantitative Health Sciences; and Harpreet Kaur, PhD, Genomic Medicine Institute.
Image: Jennifer Hockings, PharmD, PhD, BCPS (left) & Asha Kallianpur, MD, MPH (right)