Program Director/Principal Investigator (Last, First, Middle): Khush, Kiran Kaur PROJECT SUMMARY(Seeinstructions): This is an application for a K23 awardfor Dr. Kiran Khush, an instructor in cardiology and heart transplantation at Stanford University, who is establishing herself as a young investigator studying donor evaluation for heart transplantation. This K23 award will provide Dr. Khush with the support necessary to accomplish the following goals: (1) to independently design, implement, and analyze cohort study data;(2) to obtain fluency in biostatistical methodology and genetic epidemiology;and (3) to develop an independent clinical research career. To achieve these goals, Dr. Khush will work closely with her primary mentor Dr. Hannah Valantine, Director of Heart Transplant Research at Stanford, and her co-mentor Dr. Thomas Quertermous, Research Chief of the Division of Cardiovascular Medicine at Stanford. Dr. Valantine has extensive clinical research experience within the realm of heart transplantation and has a proven track record of successfully mentoring junior faculty. Dr. Quertermous is an internationally-recognized expert in cardiovascular genetics and has guided many junior faculty members towards independent careers. Heart transplantation provides the most effective treatment for end-stage heart disease. The critical deficit in suitable donor hearts, however, continues to limit transplant rates in the United States and worldwide. One solution to the donor shortage is to increase the yield of acceptable hearts from available donors through development of systematic, evidence-based criteria for donor selection. Dr. Khush will leverage the resources available at Stanford University to identify clinical and genetic risk factors for graft left ventricular dysfunction (Aim 1), to identify donor clinical and genetic predictors of poor recipient outcomes after transplantation (Aim 2), and to perform a prospective cohort study evaluating whether early post-transplant biomarkers mediate the associations between donor risk factors and recipient outcomes. This research will provide Dr. Khush with the skills and preliminary data necessary to investigate the mechanisms that modulate recipient outcomes after heart transplantation, to be proposed in an R01 grant application before the end of the K award period.

Public Health Relevance

Approximately 60% of potential donor hearts are discarded, primarily due to left ventricular dysfunction. Understanding the mechanisms responsible for graft dysfunction may facilitate the development of prevention or treatment strategies to increase the availability of donor hearts. Moreover, systematic evaluation of donor risk factors for adverse post-transplant outcomes may help to refine current donor selection criteria.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Scott, Jane
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Goldstein, Benjamin A; Thomas, Laine; Zaroff, Jonathan G et al. (2016) Assessment of Heart Transplant Waitlist Time and Pre- and Post-transplant Failure: A Mixed Methods Approach. Epidemiology 27:469-76
Khush, K K; Zaroff, J G; Nguyen, J et al. (2015) National decline in donor heart utilization with regional variability: 1995-2010. Am J Transplant 15:642-9
Khush, Kiran K; Nguyen, John; Goldstein, Benjamin A et al. (2015) Reliability of transthoracic echocardiogram interpretation in potential adult heart transplant donors. J Heart Lung Transplant 34:266-9
Khush, Kiran K; Pham, Michael X; Teuteberg, Jeffrey J et al. (2015) Gene expression profiling to study racial differences after heart transplantation. J Heart Lung Transplant 34:970-7
Chen, Sharon; Selamet Tierney, Elif Seda; Khush, Kiran K et al. (2015) Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. J Heart Lung Transplant 34:100-6
De Vlaminck, Iwijn; Khush, Kiran K; Strehl, Calvin et al. (2013) Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155:1178-87
Ginwalla, M; Pando, M J; Khush, K K (2013) Pregnancy-related human leukocyte antigen sensitization leading to cardiac allograft vasculopathy and graft failure in a heart transplant recipient: a case report. Transplant Proc 45:800-2
Khush, Kiran K; Menza, Rebecca; Nguyen, John et al. (2013) Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail 6:300-9
Khush, Kiran K; Menza, Rebecca; Nguyen, John et al. (2012) Electrocardiographic characteristics of potential organ donors and associations with cardiac allograft use. Circ Heart Fail 5:475-83
Khush, Kiran K; Kubo, Jessica T; Desai, Manisha (2012) Influence of donor and recipient sex mismatch on heart transplant outcomes: analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant 31:459-66

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