Nirmala Parajuli, DVM, Ph.D.

Nirmala Parajuli, Ph.D.Assistant Professor
Phone: (501)  526-6241
Laboratory (501) 526-7823
Email: Nparajuli@uams.edu

Education

DVM, Tribhuvan University, Nepal, 2001
MVSc, Seoul National University, S. Korea, 2005
Ph.D., Innsbruck Medical University, Austria, 2009

Research Interests

Kidney transplantation increases longevity and quality of life and reduces medical costs for patients with end-stage kidney disease, but 70% of patients will remain on dialysis due to a shortage of transplantable kidneys and many will die while on the waiting list (~40,000/year). While kidneys from living donors have better long-term outcomes, regardless of tissue match kidneys from deceased donors are more readily available. Thus, optimizing long-term graft function continues to be a challenge, especially with kidneys from deceased donors, which comprise 70% of total transplants. One key variable between living and deceased donors is preservation using cold storage (CS)—kidneys from deceased donors undergo CS for preservation (flushing and static storage in CS solution or hypothermic machine preservation at 4oC), while kidneys from living donors are generally excluded from or minimally exposed to CS. Unfortunately, prolonged CS (≥ 18 h) is detrimental to graft function after transplantation. This highlights the importance of preventing the triggers of CS-related injury, especially because more than 20% of donor kidneys are discarded or not transplanted each year in part due to CS-mediated tissue injury. Therefore, long-term interest of my laboratory is to investigate novel mechanisms by which CS induces injury in the transplants leading to the identification of novel therapeutic targets that could lead to improved renal outcome after transplantation. Specifically, we are investigating the roles of proteasome, heat shock proteins, and complement pathway during CS plus transplantation. We have established a rat kidney transplantation model, which will be fundamental in studying mechanisms of renal injury during transplantation. Decreasing the injury associated with CS could help organs be used more effectively, delay graft failure, improve long-term graft survival, and lower the mortality rates for patients with end-stage kidney disease.

Meet Dr. Parajuli’s Research Team

Recent Research Support

Current Research

Transformational Project Award (19TPA34850057)                              (7/1/2019- 6/30/2022)
Targeting Renal Immunoproteasome during Cold Storage to Improve Transplant-Associated Cardiovascular Health”
Role: Principal Investigator

NIH/R01 (DK123264-01A1)                                                                      (4/01/2021 – 03/31/2026)
“Targeting Heat Shock Protein 72 to Improve Renal Function after  Transplantation”
Role: Principal Investigator

UAMS Barton Pilot Award                                                                          (1/1/2021-12/30/2021)
“The Role of Hsp72 Chaperone in Monocyte-derived Macrophage Activation and Renal Graft Failure”
Role: Principal Investigator

 

Completed Research

Marion B. Lyon New Scientist Development Award (Arkansas Children’s Research Institute (2019- 2021)
“Targeting Immunoproteasome during Cold Storage to Improve Renal Transplant Outcome in Children”
Role: Principal Investigator

Medical Research Endowment (University of Arkansas for Medical Sciences(2019- 2020)
“Novel Role of Heat Shock Protein 72 during Renal Cold Storage plus Transplantation”
Role: Principal Investigator

COBRE CTPR  (NIH- P20GM121293 (2018- 2020)
“Complements, Heat Shock Proteins, and Proteasome Function During Renal Transplantation”
PI: Alan Tackett
Role: Junior Investigator

Scientist Development Grant (SDG) – (16SDG27600026 -American Heart Association(2016-2019)
“Ubiquitin Proteasome System, Mitochondria and Renal Cold Storage”
Role:  Principal Investigator

Barton Award 17-DN-08( UAMS (2017-2018)
Novel Role of Immunoproteaseome during Renal Cold Storage and Transplantation”
Role: Principal Investigator

Fellow-to-Faculty Award (UAMS 2016-2017)
“Role of Ubiquitin Proteasome System in Renal”
Role: Principal Investigator

TRAINING PROGRAM IN THE PATHOPHYSIOLOGY OF RENAL DISEASE (T32DK61921( 2013- 2016)
Proteasome, mitochondria and cold storage/transplantation”
Principal Investigator: Sudhir Shah
Role: Trainee

NIH  (R43DK089659-01 (2010-2011)
“Assessment of MitoQ Therapy for Cold Preservation Renal Damage”
Principle Investigator: Lee Ann MacMillan-Crow
Role:  Co-Investigator

NIH/NIDDK (RO1DK078936-(2-NCE)(2008-2015)
“Manganese Superoxide Dismutase and Renal Ischemia/Reperfusion.”
Principle Investigator: Lee Ann MacMillan-Crow
Role: Co-Investigator

Selected Publications

  1. Lo S, Blaszak RT, Parajuli N (2020). Targeting mitochondria during cold storage to maintain proteasome function and improve renal outcome after transplantation. International Journal of Molecular Sciences (Invited Review; Special Issue: Targeting Mitochondria in Aging and Disease). Int J Mol Sci. 21(10):E3506. PMCID: PMC7279041; PMID: 32429129.
  2. Lo S, Byrum SD, Tackett AJ, Parajuli N (2019). Cold storage increases albumin and advanced glycation-end-product-albumin levels in kidney transplants: A possible cause for exacerbated renal damage. Transplantation Direct. 5(6):e454. PMCID: PMC6791592; PMID: 31723591.
  3. Lo S, MacMillan-Crow, Parajuli N (2018). Renal cold storage followed by transplantation impairs proteasome function and subsequently mitochondrial protein homeostasis. American Journal of Physiology Renal Physiology. doi: 10.1152/ajprenal.00316.2018. PMCID: PMC6383197; PMID: 30303714.
  4. Parajuli N, Shrum S, Tobacyk J, Harb A, Arthur JM, MacMillan-Crow LA (2017) Renal cold storage followed by transplantation impairs expression of key mitochondrial fission and fusion proteins. PLoS ONE 12(10): e0185542. PMCID: PMC5627902; PMID: 28977005.
  5. Shrum S, MacMillan-Crow LA, Parajuli N (2016). Cold storage exacerbates renal and mitochondrial dysfunction following transplantation. Journal of Kidney. 2016 Feb;2(1). PMCID: PMC4825688; PMID: 27066594.
  6. Parajuli N and MacMillan-Crow LA (2013). Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis? Am J Physiol Renal Physiol. 304(3):F257-67. PMCID: PMC3566516; PMID: 23195678.
  7. Parajuli N, Campbell LH, Marine A, Brockbank KG, Macmillan-Crow LA (2012). MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys. PLoS One. 7(11): e48590. PMCID: PMC3490900; PMID:
  8. Parajuli N, Marine A, Simmons S, Saba H, Mitchell T, Shimizu T, Shirasawa T, Macmillan-Crow LA (2011). Generation and characterization of a novel kidney-specific manganese superoxide dismutase knockout mouse. Free Radic Biol Med. 15; 51(2):406-16. PMCID: PMC3118857; PMID: 21571061.

 

View Dr. Parajuli’s Publication List