Joseph Carcillo, MD
Disclosures: Nothing to disclose
OMB No. 0925-0046, Biographical Sketch Format Page

OMB No. 0925-0001 and 0925-0002 (Rev. 9/17 Approved Through 03/31/2020)


BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors.


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NAME: Carcillo, Joseph A Jr


eRA COMMONS USER NAME (credential, e.g., agency login): CARCILLOJA POSITION TITLE: Professor, Critical Care Medicine and Pediatrics

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

 

 

INSTITUTION AND LOCATION

DEGREE

(if     applicable)

Completion Date MM/YYYY

 

FIELD OF STUDY

 

Wesleyan Univ, Middletown, CT

Geo. Washington Univ. Sch. Med., Washington DC Geo. Washington Univ. Sch. Med., Washington DC Geo. Washington Univ. Sch. Med., Washington DC

 

B.A.

M.D.

 

06/1976

06/1982

06/1985

06/1987

 

Biology Medicine

Pediatric Residency Ped CCM Fellowship

 

A.     Personal Statement

 

My present investigations at the University of Pittsburgh, funded by a NIGMS R01 grant. are devoted to understanding the contribution of host- virus pathogen interactions to mortality from sepsis.  More than 1 of 5 global deaths from 1998 – 2017 have been attributed to sepsis.  My particular interest is in the contribution of virus induced hyperferritinemic sepsis to morbidity and mortality.  This interest drew me to develop collaborations with Dr Jeremy Prokop and Dr Surender Rajasekeran of Michigan State University.  In lieu of the new pandemic we have developed a structural and evolution dynamic database of the SARS-CoV-2 proteome which we have publicly released (https://drive.google.com/open?id=1dXBJpLo3bay1JQ9BckUsVcTViv6P0w1q)Here we provide access to public use gene variant and protein databases related to SARS-CoV-2 virus, and also to the human and 235 non-human species hosts. These databases allow us to gain molecular insights into 1) how SARS-CoV-2 binds and is internalized into human and non- human host cells and tissues; 2) how SARS-CoV-2 inhibits the ability of the host cells to kill the virus; and 3) how the virus transforms host cell genetic machinery down a deleterious auto-inflammatory path leading to increased pathogenicity, hyperferritinemia, and death. 

 

Because gene variants are unevenly distributed across gender, race and ethnicity groups, we can use these databases to mathematically predict differences in gender, race and ethnicity based susceptibility to SARS-CoV-2 infection and spreadingI recently received the Notice Of Special Interest (NOSI) (NOT-GM-20-025) to address the urgent need for research on the SARS-CoV-2 virus asking for incorporation of data related to SARS-CoV-2 into ongoing research efforts to develop predictive models for the spread of SARS-CoV-2 and other related infectious agents. We propose to answer this request developing mathematical models predicting differential spreading of SARS-CoV-2 in at risk groups including males, African Americans, Native Americans, and Hispanics.

 

Positions and Honors Positions and Employment

 

 

 

 

George Washington University School of Medicine, Washington, D.C.

1987-1988              Staff Intensivist , Children's Hospital National Medical Center, Washington, D.C.

1988-1992              Pediatric Staff , Ntl Hlth Serv Corps, U.S. Civil Service Branch, USPHS, Pediatrics, Ft Pierce, FL

1992-present   Assoc Dir, Ped Intensive Care Unit, Dept Anesthesiology/CCM, Children's Hosp of Pgh,   Pittsburgh, PA

1992-2002                    Asst Prof, Dept Anes/CCM , Univ Pittsburgh, Pittsburgh, PA

7/2002-2003      Asst Prof, Critical Care Medicine, Children’s Hosp of Pgh, Pittsburgh, PA

1992–2003        Asst Prof, Dept of Pediatrics, Children’s Hosp of Pgh, Pittsburgh, PA

2003-2012              Assoc Prof, Critical Care Medicine & Pediatrics, Children’s Hosp of Pgh of UPMC, Pgh, PA 4/2012- present Prof, Critical Care Medicine & Pediatrics, Children’s Hosp of Pgh of UPMC, Pgh, PA

 

Other Experience and Professional Memberships

1986

Society of Critical Care Medicine

1995

Fellow, American Academy of Pediatrics

1997

Society for Pediatric Research

2000-2015 Newborn and Pediatric Study Section NICHD (SO R Anand), Ad HOC reviewer SEP (SO J Firrell),

Ad hoc reviewer STTR/SBIR (SO J Firrell)

2004              Member of NIAIID roundtable for Prioritization of Emergency Medicine Research Agenda (SO J Firrell)

2010              Invite speaker SOS of Transfusion Medicine NHLBI (SO T Mondoro)

2015              Invited steering committee SOS Pediatric Multiple Organ Dysfunction NICHD (MO R Tamburro) 2016              Advisor to Medicines Sans Frontieres Pediatric Days

 

Honors

1976              High Honors Thesis in Biology, Wesleyan University Honor College 1982              Sandoz Psychiatry Award, George Washington University

1982              Lange Publication Award, George Washington University

1982              Alpha Omega Alpha Honor Society, George Washington University 1987              Society of Critical Care Medicine In-Training Award, SCCM

1988              Burton Epstein Award for Outstanding Fellow in Pediatric Critical Care Medicine, Child Ntl Med Ctr, Wash, DC

1997-2002 Society for Critical Care Medicine Presidential Citation Awards 1998              Society for Critical Care Medicine Program Committee (Co-Chair) 2002-present Best Doctors in America

2002-present Who’s Who in America

 

B.     Contributions to Science

 

1.  Developed Scientific Basis of and Chaired Taskforce Clinical Practice Parameters for Management of Newborn and Pediatric Septic Shock. From 1991 to 2002, our research in septic shock defined specific differences between children and adults including the following 1) children with septic shock commonly benefit from fluid resuscitation(1a) 2) children with septic shock commonly have low cardiac output and not uncommonly have elevated pulmonary and systemic vascular resistance and therefore respond to inotropes, vasodilators, and ECMO(1b), 3) children with septic shock commonly have adrenal shock which respond to hydrocortisone(1c). Based on this research I was asked to and did chair the taskforce which wrote the American College of Critical Care Medicine and American Heart Association sanctioned guidelines for Hemodynamic Support of Newborns and Children with Septic Shock(1d). Our concomitant epidemiologic work demonstrated the importance of sepsis as a leading cause of death in children and emphasized the importance of these guidelines to child health (1k,l).

 

1a) Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA. 1991 Sep 4;266(9):1242-5. PMID:1870250

1b) Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in fluid-refractory pediatric septic shock.Pediatrics. 1998 Aug;102(2):e19.PMID:9685464

1c) Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock. Crit Care Med. 2005 Apr;33(4):855-9. PMID:15818116

1d) Carcillo JA, Fields AI; American College of Critical Care Medicine Task Force Committee Members. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med. 2002 Jun;30(6):1365-78. Review.PMID:12072696

 

1.Elucidating Mechanisms of Inflammation induced Multiple Organ Failure in Pediatric Sepsis From 1996 to 2015 our research group determined that systemic inflammation leads to Multiple Organ Dysfunction in pediatric sepsis). We characterized three sepsis specific inflammation pathobiology phenotypes (2ad) Immunoparalysis (an immune dysfunction process marked by an inability to kill microbes due to an inadequate Th1 response), Thrombocytopenia Associated Multiple Organ Failure (an thrombotic microangiopathy marked by an inability to resolve vWF multimer microvascular thrombi due to ADAMTS 13 deficiency), and Sequential Multiple Organ Failure (a liver failure associated process mediated by sFasL release from lymphocytes due to failed CTL and NKL cell mediated apoptosis of virus associated lymphoproliferative disease). Our research group also developed phenotype specific therapies to inform individualized medicine for children.

2a) Felmet KA, Hall MW, Sclar RS, Jaffe R, Carcillo JA. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. J Immunol; 174(6):3765-3772. PMID:15749917; 2005

2b) Hall MW, Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, Carcillo JA. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med. 2011 Mar;37(3):525-32. Epub 2010 Dec 10. PMID: 21153402 [PubMed - indexed for MEDLINE]

2c) Nguyen TC, Han YY, Kiss JE, Hall MW, Hassett AC, Jaffe R, Orr RA, Janosky J Carcillo JA. Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure. Crit Care Med; 2008 36(10):2878-2887. PMCID: PMC2772176; 2008

2d) Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, Cron RQ, Opal SM. Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of

Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial.Crit Care Med. 2016 Feb;44(2):275-81. doi: 10.1097/CCM.0000000000001402.PMID:26584195

2e)Carcillo JA, Berg RA, Wessel D, Pollack M, Meert K, Hall M, Newth C, Lin JC, Doctor A, Shanley T, Cornell T, Harrison RE, Zuppa AF, Reeder RW, Banks R, Kellum JA, Holubkov R, Notterman DA, Dean JM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.Pediatr Crit Care Med. 2019 Dec;20(12):1137-1146. doi: 10.1097/PCC.0000000000002105.PMID:31568246

 

 

2.  Developing International Guidelines for Management of Pediatric Severe Sepsis and Multiple Organ Failure. I have also worked from 2005-2015 in the development of the Global Pediatric Sepsis Initiative for resource specific management of Pediatric Severe Sepsis. Sepsis is the leading global killer of children under five with the majority of these children living in resource poor settings.

3a) Kissoon N, Carcillo JA, Espinosa V, Argent A, Devictor D, Madden M, Singhi S, van der Voort E, Latour J; Global Sepsis Initiative Vanguard Center Contributors. World Federation of Pediatric Intensive Care and Critical Care Societies: Global Sepsis Initiative Pediatr Crit Care Med. 2011 Sep;12(5):494-503. doi: 0.1097/PCC.0b013e318207096c.PMID:21897156

3b) Mangia CM, Kissoon N, Branchini OA, Andrade MC, Kopelman BI, Carcillo J. Bacterial sepsis in Brazilian children: a trend analysis from 1992 to 2006. PLoS One. 2011;6(6):e14817. doi: 10.1371/journal.pone.0014817. Epub 2011 Jun 3.PMID:21674036

 

3.  Supporting studies in the NICHD Collaborative Pediatric Critical Care Research Network Qualitative research experience. Since 2004 I have supported over 98 published clinical pediatric studies in the Eunice Kennedy Shriver National Institute of Child Health and Development Collaborative Pediatric Critical Care Research Network.

 

Complete List of Published Work of 295 (Pubmed) peer reviewed publications http://www.ncbi.nlm.nih.gov/pubmed/?term=carcillo

 

C.     Additional Information: Research Support and/or Scholastic Performance Ongoing Research Support

NIH-1R01GM108618-01              (Carcillo)              6/1/19 – 5/30/23

Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure

This study evaluates the presence of inflammation phenotypes in pediatric sepsis induced MOF. Role: PI

 

NIH UG1 HD049983-15              (Carcillo)              12/24/14 11/30/20

Renewal of Collaborative Pediatric Critical Care Research Network (CPCCRN)

The major goals of this project are to establish a national research network to perform studies of critically ill children.

Role: PI

 

NIH 1R01 GM113838 (Doctor)              6/1/15 – 1/31/20

Washington University

Sepsis-Induced Red Cell Dysfunction, SIRD

The goals of this project are to fully characterize SIRD as a (yet undescribed) distinct organ failure impairing O2 delivery in sepsis, to elucidate SIRD’s role in multiple organ failure (MOF) progression, and to evaluate a mechanism-based therapy targeted to SIRD pathobiology.

Role: Co-Investigator

 

Completed Research Support (Past Three Years)

 

 

NIH-R01HD073362 (Zimmerman) 9/25/13-6/30/18

Seattle Children’s Hospital

Life After Pediatric Sepsis Evaluation, LAPSE

The primary objectives of this application are to comprehensively characterize HRQL/FS outcomes and to critically examine the potential clinical risk factors for sepsis-associated HRQL/FS deterioration.

Role: Co-Investigator

 

NIH-1R01GM108618-01              (Carcillo)              3/1/14 – 2/28/19

Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure

This study evaluates the presence of inflammation phenotypes in pediatric sepsis induced MOF. Role: PI