Hrishikesh S. Kulkarni, M.D., MSCI

Assistant Professor
Internal Medicine
Pulmonary & Critical Care
Molecular Microbiology

Molecular Microbiology and Microbial Pathogenesis Program
Immunology Program
Molecular Cell Biology Program

Research Abstract:

Dr. Kulkarni’s research focuses how the innate immune system, specifically complement proteins, affects the lung epithelium in health and disease. During postdoctoral training with Dr. John Atkinson (Rheumatology), he demonstrated that airway epithelial cells are unique in having intracellular stores of the complement protein C3 (a central component of the cascade) and these stores can be augmented to mitigate cell death. Dr. Kulkarni employs both in vitro and in vivo model systems to distinguish the role of locally-derived C3 in the lung from that present in the blood and how it modulates the development of acute lung injury.

Additionally, Dr. Kulkarni is utilizing human bronchoalveolar lavage specimens, explant tissue and DNA to determine whether certain components of the complement system can be used to identify those recipients developing severe primary graft dysfunction, a form of acute lung injury occurring after lung transplantation.

The overarching goal of this research is to determine how epithelial cell-derived proteins can be harnessed to mitigate the risk of acute lung injury in various settings, to ultimately reduce the burden of end-stage lung disease. Additionally, identifying mechanisms by which complement facilitates survival of airway epithelial cells makes it an attractive target for studying in other diseases benefiting from pro-survival mechanisms such as cancer.

Mentorship and Commitment to Diversity Statement:
My commitment to promoting diversity and inclusion in academics has developed based on my personal experience, starting from my medical school in India, and the opportunities that I have been fortunate to receive throughout my career. As a first-generation immigrant, I am acutely aware of the challenges of settling in a new country, and being provided with the right environment to thrive, as the stakes can be high. As a result, from the onset, our laboratory has aimed to recruit diverse candidates at every level, across race, ethnicity and citizenship status. In my role as the Associate Program Director for Research in the Division of Pulmonary and Critical Care Medicine, I continually evaluate how we can make our training program better and more inclusive, as through this process, everyone benefits from differing perspectives. We have implemented programs at the recruitment level, and at all stages of training, to help accomplish these goals. Moreover, I have facilitated the development of an individualized mentorship program to help bring out the best in our trainees and have been able to partner with other faculty to together accomplish this objective, thus, helping accomplish their overall career goals.

Selected Publications:

Elvington ME, Liszewski MK, Bertram PL, Kulkarni HS, Atkinson JP, A C3(H2O) recycling pathway of the intracellular complement system. J Clin Invest 2017: 127: 970-81.

Kulkarni HS, Elvington M, Perng YC, Liszewski MK, Frakouh CS, Byers DE, Yusen RD, Lenschow DJ, Brody SL, Atkinson JP, Intracellular C3 protects human airway epithelial cells from stress-induced cell death. Am J Resp Cell Mol Biol 2019; 60: 144-57.

Elvington M, Liszewski MK, Liszewski AR, Kulkarni HS, Hachem RR, Mohanakumar T, Kim AHJ, Atkinson JP. Development and optimization of an ELISA to quantitate C3(H2O) as a marker of human disease. Front Immunol 2019; 10:703.

Scozzi D, Ibrahim M, Liao F, Lin X, Hsiao HM, Hachem R, Tague L, Ricci A, Kulkarni HS, Huang HJ, Sugimoto S, Krupnick AS, Kreisel D, Gelman AE. Mitochondrial damage associated molecular patterns released by lung transplants are associated with primary graft dysfunction. Am J Transplant 2019;19:1464-77.

Kulkarni HS, Ramphal K, Ma L, Brown M, Oyster M, Speckhart KN, Takahashi T, Byers DE, Porteous MK, Kalman L, Hachem RR, Rushefski M, McPhatter J, Cano M, Kreisel D, Scavuzzo M, Mittler B, Cantu E 3rd, Pilely K, Garred P, Christie JD, Atkinson JP, Gelman AE, Diamond JM. Local complement activation is associated with primary graft dysfunction after lung transplantation. JCI Insight. 2020;5:e138358.

Scozzi D, Cano M, Ma L, Zhou D, Zhu JH, O'Halloran JA, Goss C, Rauseo AM, Liu Z, Sahu SK, Peritore V, Rocco M, Ricci A, Amodeo R, Aimati L, Ibrahim M, Hachem R, Kreisel D, Mudd PA, Kulkarni HS*, Gelman AE* (co-corresponding author). Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight. 2021;6:e143299.

Last Updated: 4/1/2021 6:50:32 AM

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