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4/20/2021 - Medical Grand Rounds: Special K Club Series -DAMP's, Drugs, Degradation; Virtual HLA crossmatch; and understanding the role of lysine acetylation





Credit Hours: CME 1.00

Target Audience:

Faculty, residents, fellows, and community physicians in General Internal Medicine and subspecialties.

DAMP's, Drugs, Degradation: Targeting Protein Degradation Pathways that Regulate Innate Immunity in Acute Lung Injury
Presented by: John Evankovich, III, MD
Virtual HLA crossmatch to improve efficiency of kidney allocation and organ placement
Presented by: Chethan Puttarajappa, MD

Understanding the role of lysine acetylation in regulation of cardiac energy metabolism
Presented by: Dharendra Thapa, PhD

Educational Objectives:

Upon completion of this activity, participants should be able to:

  • Recognize the contribution of Damage Associated Molecular Patterns to Innate Immune Activation
  • Review how protein degradation may be used to modulate innate immune pathways in lung injury
  • Assess how drug screening based on protein abundance could be a tool to discover new therapeutics in lung injury
  • Describe kidney organ acceptance by better recognition of false positive cell-based HLA crossmatch
  • Determine reliability of virtual HLA crossmatch for kidney transplant candidates by obtaining accurate sensitization history
  • Evaluate health resource utilization by judicious use of virtual HLA crossmatch for deceased donor kidney transplantation
  • Improve patient outcomes by avoiding prolonged cold ischemia time in deceased donor kidney transplantation
  • Examine access to kidney transplant by optimizing virtual HLA crossmatch use for deceased donor kidney transplantation
  • Assess the impact of acetylation in regulating mitochondrial protein function.
  • Investigate the role of GCN5L1 in regulating the function of fatty acid oxidation proteins.
  • Review the role of GCN5L1 in improving heart function with age.

Suggested Additional Reading & Joint Accreditation Statement - Note: This Accreditation Statement Supersedes All Other Statements:

Suggested additional reading:

  1. Tong, Yao, et al. The RNFT2/IL-3R axis regulates IL-3 signaling and innate immunity. JCI insight 5.3 (2020).
  2. Evankovich, John, et al.  Toll-like receptor 8 stability is regulated by ring finger 216 in response to circulating microRNAs.  Am J Respiratory Cell and Mol Bio. 62.2 (2020) 156-167.
  3. Matthay, MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers 5, 18 (2019). 
  4. DF Pinelli, AR Tambur. Virtual crossmatching for deceased donor transplantation: one size does not fit all. Kidney International 2020 Vol. 97 Issue 4 Pages 659-662.
  5. M. Kamoun, D. Phelan, H. Noreen, et. al. HLA compatibility assessment and management of highly sensitized patients under the new kidney allocation system (KAS): A 2016 status report from twelve HLA laboratories across the U.S. Hum Immunol 2017 Vol. 78 Issue 1 Pages 19-23.
  6. S. Shrestha, L. Bradbury, M. Boal, et al. Logistical Factors Influencing Cold Ischemia Times in Deceased Donor Kidney Transplants. Transplantation 2016 Vol. 100 Issue 2 Pages 422-8.
  7. Thapa D et al. Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function. Current Research in Physiology 2020 Dec;3(44-49).
  8. Thapa D et al. Cardiomyocyte-Specific Deletion of GCN5L1 in Mice Restricts Mitochondrial Protein Hyperacetylation in Response to a High Fat Diet. Scientific Reports 2020 Jun 30;10(1):10665. 
  9. Thapa D et al. Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart. Am J Physiol Heart Circ Physiol. 2017 Aug 1;313(2):H265-H274. 

Joint Accreditation Statement
In support of improving patient care, the University of Pittsburgh is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME) and the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

The University of Pittsburgh School of Medicine designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit[s]™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This educational activity is approved for 1.0 contact hours.

Other health care professionals will receive a certificate of attendance confirming the number of contact hours commensurate with the extent of participation in this activity.

Chethan Puttarajappa, MD — Assistant Professor of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine
No relationships with industry relevant to the content of this educational activity have been disclosed.
Dharendra Thapa, PhD — Postdoctoral Research Fellow, Vascular Medicine Institute, University of Pittsburgh School of Medicine
No relationships with industry relevant to the content of this educational activity have been disclosed.
John Evankovich, III, MD — Assistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine
No relationships with industry relevant to the content of this educational activity have been disclosed.
No other members of the planning committee, speakers, presenters, authors, content reviewers and/or anyone else in a position to control the content of this education activity have relevant financial relationships with any companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

This activity is approved for AMA PRA Category 1 Credit™

The University of Pittsburgh is an affirmative action, equal opportunity institution.