Bartley P. Griffith, MD

1970    B.S. Biology  - Bucknell University                 

1974    M.D. Medicine - Jefferson Medical College  (Sidney Kimmel Medical College)

Post Graduate Education

1974-1975  Intern, Surgery, University of Pittsburgh SOM, Pittsburgh, Pa                                         

1975-1977  Resident, General & Cardiothoracic Surgery, University of Pittsburgh, SOM. Pittsburgh, PA                

1977-1978  Research Fellow, University of Pittsburgh, SOM, Pittsburgh, PA                                                            

1978-1979  Resident, General & Cardiothoracic Surgery, University of Pittsburgh, SOM, Pittsburgh, PA              

1979-1981  Chief Resident, Cardiothoracic Surgery,  University of Pittsburgh, SOM. Pittsburgh, PA                   

NAME:  Bartley P. Griffith

eRA COMMONS USER NAME (credential, e.g., agency login):   griffithbp

POSITION TITLE:  Professor of Surgery with Tenure

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.)

PERSONAL STATEMENT

Over my career, my clinical and investigational work has focused on the treatment of heart and lung end-stage diseases. I have approached that task by combining heart and lung transplantation with the developments in total artificial heart, ventricular assist devices, ECMO, and now ambulatory ECMO.  To do so, I established the McGowan Center for Artificial Organ Development at the University of Pittsburgh, which was a $10 million philanthropic effort resulting in the multi-use free-standing facility.  I have continued my investigative work and, since 1986, have been continuously funded as a principal investigator by the NIH.  Work continued in an ambulatory artificial lung, which first was funded in 1990, and has used more than $20 million of NIH support.  The device once imagined on a napkin is now cleared by the FDA for clinical use, and the role-out of the Breethe system designed for home use will begin in the next few months.  The work on this system evolved with clinical input from experiences in patients with end-stage respiratory distress but also included multi-disciplinary input from a broad array of experts in the bioengineering aspects of the project.  Recently, my funding has extended to include clinical program director for xenotransplantation of the heart.  This program’s ongoing focus has been the outcome in genetically engineered swine hearts when placed in baboons.  Success with that program (survivals in excess of 150 days and ongoing) suggests that clinical implementation may be appropriate soon.  Throughout my career I have been a mentor of cardiothoracic surgical trainees and other post doc engineers.

POSITIONS AND HONORS

Positions and Employment

•     Assistant Professor of Surgery, University of Pittsburgh, Department of Surgery, Pittsburgh, PA.

•      Associate Professor of Surgery, University of Pittsburgh, Department of Surgery, Pittsburgh, PA

1988-2001     Professor of Surgery, University of Pittsburgh, Department of Surgery, Pittsburgh, PA.

1990-2001      The Henry T. Bahnson Professor of Surgery

2001-2012      Professor of Surgery, Chief of Cardiac Surgery, UMMC, Department of Surgery, Baltimore, MD

2003-2007      Bioengineering graduate faculty, University of Maryland, College Park

2007-present  Adjunct Professor, Bioengineering, University of Maryland, College Park

2008-present  The Thomas E. and Alice Marie Hales Distinguished Professor, University of Maryland SOM

Other Experience and Professional Memberships

1982 – present                 International Society for Heart and Lung Transplantation

1984 – present                 Society of Thoracic Surgeons

1984 – present                 Fellow, American College of Surgeons

1985 – present                 Society of University Surgeons

1985 – present                 American Association for Thoracic Surgery

1988 – present                 American Surgical Association

2002 – present                 Cardiac Surgery Biology Club

2002 – present                 Southern Thoracic Surgical Association

1993-1997              NIH - Surgery, Anesthesiology and Trauma Study Section, Division of Research Grants                              

1998                       NHLBI Board of Scientific Counselors                                                                           

• Immunosuppressant Drugs Subcommittee of the Standing Antiviral Drugs Advisory Committee
• NIH Special Emphasis Panel for Review of RFA: HL-98-077: Specialized Centers of Research in Ischemic Heart Disease                                                                             
• NIH/NHLBI Scientific Frontiers in Cardiothoracic Surgery     

2001                                        Chair, NIH SEP for RFA AI-00-013:  Immunopathogenesis of Chronic Rejection (2/7-9/01)

2001-2002                               NIH SEP for Bioengineering Research Partnership Applications PAR-03-032                                   

2004                            NIH SEP for SRA, Hypertension & Microcirculation Study Section 1 R01 HL080501-01

2005                            NIH Special Emphasis Panel                                                                                                                                    

2006                       NHLBI Strategic Planning Process – Cardiovascular Program, Theme #7:  Working Group:  Emerging and Evolving Technologies

2007                      NIH Biomaterials & Bio-interfaces Study Section 1 R01 HL092166-01                               

2009-2011             Chair, AATS Scientific Affairs and Government Relations Committee

2009                      NIH College of CSR Reviewers                                      

2013                      NIH Biomaterials & Bio-interfaces SS      2R01 HL120975-01 & 1R01 HL121057-01

2014                      NIH Bioengineering, Technology, and Surgical Sciences (BTSS)

2015                                        NIH Special Emphasis Panel:  Translational Programs in Lung Diseases (tPPG)

2017                      NHLBI Review:  RFA HL-17-015 Bold New Bioengineering Methods and Approaches

2017                      NIH Special Emphasis Panel/Scientific Review Group/05/ ZRG1 CVRS-Q (11)                                        

2017                      AATS/NHLBI 2017 Workshop June 25-27, 2017, Bethesda, MD. Identifying Collaborative Clinical Research Priorities in Lung Transplant

2018                            NIH Small Business Applications:  CV Respiratory Sciences (ZRG1 CVRS-Q 11B)

2018-2019             NHLBI Data & Safety Monitoring Board (DSMB) for the Prevention of Lung Transplant Injury with Regadenoson

Honors

1992 The Fred Brand Jr. Visiting Professor Lectureship, Pittsburgh, PA

1994 Ormand C. Julian Visiting Professorship, Rush-Presbyterian-St. Luke’s Med Center, Chicago, IL

1996 The William B. Ford Lecture in Cardiac Surgery, Shadyside Hospital, Pittsburgh, PA

1998  Induction into the Royal College of Surgeons, Edinburgh, Scotland, UK

1999 14^th Annual Dennison Young Memorial Symposium, Albert Einstein College of Medicine, NY, NY

2000 Tom Williams Lecture, University of Alberta, Edmonton, Alberta, Canada

2003 Editorial Board – Journal of Thoracic & Cardiovascular Surgery

2008  Board of Regents Faculty Award for Research, Scholarship, Creative Activity, U of MD, Baltimore

2008  Thomas E. and Alice Marie Hales Distinguished Professor, U of MD School of Medicine

2009  R Adams Cawley Shock Trauma Hero Award:  Dedication & Outstanding Contribution to Saving Lives

2009  Latner Lecture, Development of the Artificial Lung, University of Toronto 

2009  Invited Speaker 3^rd Ann James A. Magovern Memorial Lecture, New Inspiration for Artificial Respiration

2010  University of Maryland, Founders Week Award:  Faculty Research Lecturer of the Year

2011  R. Adams Cowley Shock Trauma Hero Award:  Dedication & Outstanding Contribution to Saving Lives

2013   R. Adams Cowley Shock Trauma Hero Award:  Dedication & Outstanding Contribution to Saving Lives

2015   Author of featured landmark article (Ann Thorac Surg 1987;43:6-16) in the Annals of Thoracic Surgery, October 2015 issue.  Commentary by Joel D. Cooper, M.D. (Ann Thorac Surg 2015;100:1151-4)

2016   Buxton Lecture: “Hickory Dickory Doc – Returning to a Beginner’s Mind” University of Maryland School of Medicine Surgical Grand Rounds.  Dr. Robert W. Buxton Lecture & Symposium – June 23, 2016

2017  Entrepreneur of the Year, University of Maryland School of Medicine

2019  Annual Henry T. Bahnson Lecture: Hank Bahnson:  A Gatherer and Enabler of Genius.  University of Pittsburgh Medical Center, Pittsburgh, PA  May 14, 2019

2020 Walton Lillehei Lecture:   Bumper Car Innovation of Heart Pumps and Mechanical Lungs

STS 56^th Annual Meeting, New Orleans, LA  01/28/20

2020  Innovation Award in Mechanical Circulatory Support   Implantable Artificial Lung I American Association for Thoracic Surgery’s Mechanical Support for the Heart and Lung Symposium: New Devices and Techniques Houston, TX February 14-15, 2020

Contribution to Science

Xenotransplantation

I am Co-Director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine.  I am principal investigator of the clinical program for the more than $23 million effort.  The sponsor, United Therapeutics, has vested in the University of Maryland and, in part, my leadership to approach humanized swine hearts as substitutes for human organ heart donation.  Currently, we have had an exciting degree of success with four baboons, all concurrent, surviving between 50 and 150 days.  We hope to reach a threshold of six months for six animals to ensure the possibility of FDA approval of a clinical effort.  In the meantime, we are planning for implantation of a heart in a deceased human for a short 48-hour period.  This will be done to further clarify work that cannot be understood well in the small baboon transplant.  Also, it is necessary to account for human anti-pig antibodies that do not exist in the baboon species.  We need to test our genetic manipulation of the swine heart to assure that it is.

• Goerlich CE, Griffith B, Kaczorowski D, Singh A, Abdullah M, Lewis B, Zhang, T, Tatarov I, Sentz F, Hershfeld A, Levy P, Odonkor B, Williams E, Strauss E, Tabatabai A, Bhutta A, Ayares D, and Mohiuddin M. Human transgenes influence cardiac xenograft survival in orthotopic pig-to-baboon model.  J Intl Heart Lung Trans, 2020
• Goerlich, C, Kaczorowski D, Singh A, Abdullah M, Lewis B, Zhang T, Tatarov I, Sentz F, Hershfeld A, Odonkor B, Williams, Strauss E, Ayares D, Griffith B, and Mohuiddin M. Human thrombomodulin transgene expression prevents intracardiac thrombus in life-support pig-to-baboon cardiac xenotransplantation (podium presentation) ISHLT, Montreal, Canada April 22, 2020
• Griffith BP, Goerlich CE, Singh AK, Rothblatt M, Lau CL, Shah A, Lorber M, Grazioli A, Saharia KK, Hong SN, Joseph SM, Ayares D, and Mohiuddin M. Genetically modified Porcine-to-human cardiac xenotransplantation.  N Engl J Med; DOI: 10. 1056/NEJMoa2201422, June 22, 2022 at NEJM.org.

Development of Immunosuppression for Heart and Lung Transplantation

Soon after I joined the faculty at the University of Pittsburgh, Dr. Thomas Starzl joined Dr. Henry Bahnson in a pan transplant effort.  Because Starzl brought the powerful new immunosuppressant cyclosporine with him, our center became only the second in the United States to have the opportunity to test the immunosuppressant in heart and lungs.  The work that occurred was foundational to the current treatment regimens.  At that time, it was impossible to use blood levels as they did not exist, and there was much clinical and seat-of-the-pants tinkering.  As things emerged and medium-term outcomes for lung transplantation did not meet those of heart transplantation, I experimented with inhalational cyclosporine.  An NIH grant was awarded for the work we had done in animals in inhalational studies, and a human trial was initiated which was published in the New England Journal of Medicine.  Currently, inhalational cyclosporine has been introduced by an Italian company as beginning widespread trials.  Much as cyclosporine was given a pathway in Pittsburgh, so was tacrolimus, again based on Dr. Thomas Starzl’s deep intuition and connections in the drug industry.  Again, I was able to initiate trials in both heart and lung recipients. 

• Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med 2006 Jan 12;354(2):141-50
• Griffith BP, Hardesty RL and Bahnson HT: Powerful but limited immunosuppression for cardiac transplantation with cyclosporines and low-dose steroid.  J Thorac Cardiovasc Surg 1984;87(1):35-42
• Armitage JM, Kormos RL, Morita S, Fung J, Marrone GC, Hardesty RL, Griffith BP and Starzl TE: Clinical trial of FK 506 immunosuppression in adult cardiac transplantation.  Ann Thorac Surg 1992;54:2:205-11
• Griffith BP, Hardesty RL, Deeb GM, Starzl TE and Bahnson HT:  Cardiac transplantation with cyclosporine A and low-dose prednisone.  Ann Surg 1982196:324-329
• Griffith BP, Goerlich, C, Singh A, Rothblatt M, Lau C, Shah A, Lorber M, Grazioli A, Saharia KK, Hong SN, Joseph SM, Ayares D, and Mohiuddin MM. Genetically modified porcine-to-human cardiac xenotransplantation.  NEngJMed, DOI 10.1056/NEJMoa2201422

Respiratory Assist

My earliest research endeavors explored 1) the possibility of arteriovenous membrane oxygenation to heal injured lungs and 2) an artificial placenta.  This work was complimented by establishment of a very early program of ECMO in 1978 at the Children’s Hospital of Pittsburgh.  Some “clinical” firsts included support of lung hypoplasia associated with diaphragmatic hernia and postsurgical cardiopulmonary failure.   Soon interest in severe lung failure led to the development of a larger clinical program in heart-lung and lung transplantation.  Innovative work included the original broad introduction of calcineuron inhibitors (cyclosporine and tacrolimus) to the lung transplant field, development of auto-perfusion of heart-lung blocs for distant procurement of donor organs, and treatment of cystic fibrosis with lung transplantation.  With inadequate numbers of donor organs for transplantation available, once again interest turned to bioengineered artificial lungs.  Since 2000, I have been principal investigator on a series of NIH awards focused on the development of adult and pediatric respiratory assist devices.  Most recently the awards included support for a clinical device designed for home use.  Key to the development has been partnerships with bioengineers and emphasis on use of computer-aided design to maximize biocompatibility of flow paths.  The device was licensed to Breethe, a UMD spinoff.  Breethe was acquired by Abiomed in Spring of 2020.  FDA approved for the device has been received and commercialization has begun.

a)  Griffith BP, Carroll RG, Hardesty RL, Peel RL, and Borovetz HS:  Selected lobar injury following infusion of oleic acid.  J Appl Physiol  1979;47:706

b)   Hardesty RL and Griffith BP:  Autoperfusion of the heart and lungs for preservation during distant procurement.  J Thorac Cardiovasc Surg  1987;93:11-18

c)  Wu ZJ, Taskin ME, Zhang T, Griffith BP. Computational Model-Based Design of a Paracorporeal Artificial Pump-Lung for Cardiopulmonary/Respiratory Support. Artif Organs. 2012 Apr;36(4):387-99. doi: 10.1111/j.1525-1594.2011.01369.x. [Epub ahead of print] PMID:  22145732

d)   Wu ZJ, Zhang T, Bianchi G, Wei X, Son H-S, Zhou K, Taskin ME, Wang P, Bianccuci B, Garcia J, Griffith BP. 30-Day In-vivo Performance of a Wearable Artificial Pump-Lung for Ambulatory Respiratory Support. Ann Thorac Surg. 2012 Jan;93(1):274-81

Mechanical Cardiac Assist

Upon completion of my residency training, I inherited the embryonic cardiac transplantation program at the University of Pittsburgh.  Soon I advanced the field with studies of novel immunosuppressants (cyclosporine and tacrolimus).  The program built a reputation for treating the most morbidly ill transplant candidates.  Due to inadequate donor hearts, I began exploring the use of mechanical substitutes and was an early user of the Jarvik Total Artificial Heart.  The team of surgeons and engineers learned much about the abnormal physiology of the human-device interface.  Soon we were exploring ventricular assist devices through their development in the laboratory and in the clinic.  I was among the original surgical team to implant the world’s first HeartMate II small format axial flow pump in a human after its development in part in our laboratory (became the market leader).  I continue to prioritize miniaturization of blood pumps for adults and children.  Recently our team has explored the impact beyond hemolysis on the blood’s formed elements as we try to understand optimum biocompatibility design.

• Griffith BP, Hardesty RL, Kormos RL, Trento A, and Borovetz HS: Temporary use of the Jarvik-7 total artificial heart prior to transplantation.  N Engl J Med 1987;316:130-134
• Macha M, Litwak P, Yamazaki K, Kameneva M, Kerrigan JP, Antaki JF, Butler KC, Thomas DC, Taylor LP, Kormos RL, Griffith BP and Borovetz HS. Survival for up to six months in calves supported with an implantable axial flow ventricular assist device. ASAIO J 1997;43:311-315
• Zhang T, Taskin ET, Fang HB, Pampori A, Jarvik R, Griffith BP, Wu ZJ. Study of Flow-induced Hemolysis using Novel Couette-Type Blood-Shearing Devices. Artificial Organs 2011 Dec;35(12):1180-6.
• Chen Z, Mondal NK, Ding J, Gao J, Griffith BP, Wu ZJ. Shear-induced platelet receptor shedding by non-physiological high shear stress with short exposure time: Glycoprotein Ibα and glycoprotein VI. Thromb Res. 2015 Apr;135(4):692-8. doi: 10.1016/j.thromres.2015.01.030. Epub 2015 Feb 7. PMID: 25677981

Education

I have been a Program Director for residency training between 1990-2018.  During this period, the entire concept as to how to better train and prepare residents for a life in cardiothoracic surgery has evolved.  On locating in Maryland in 2001, I found the residency program to be underperforming.  Consequently, I embraced the American Board of Thoracic Surgery’s initiative to test an integrated six-year training program in cardiothoracic surgery that would begin immediately following medical school.  This program attracted remarkably academic, accomplished, and committed graduates.  During this initial period, we worked hard to create a curriculum that would add critical components to a trainee’s life/work balance, not possible in a non-integrated training program.  We added a two period of non-elective academic enrichment to follow the third academic year.  In this two-year period, trainees usually entered a T32 grant structure that gave them the opportunity to complete a Master’s in Clinical Trials work.  The laboratory’s expanded during a similar period, and 4-5 of our faculty could offer significant experiences either in translational or bench work.  The graduating trainees have chosen predominately academics for their initial job,

and they have been highly attractive to the most competitive programs searching for new graduates.

• Griffith BP. The Eggs May Be Teaching the Chickens.  Kent Trinkle Lecture on Education: Ann Thorac Surg, 2013;96:1520-4 http://dx.doi.org/10.1016/j.athoracsur.2013.05.121 
• R01HL 118372-06A10 Griffith/Wu (Col-PIs)               07/01/20-05/31/24

Complete list of published work in My Bibliography (Pubmed Indexed):

http://www.ncbi.nim.nih.gov/sites/myncbi/collections/public/1PgT7IEFIAJBtGMRDdWFm/WAO/?sorted

Additional Information:  Research Support and/or Scholastic Performance

Ongoing Research Support

Enhancement of an Artificial Lung for Ambulatory Respiratory Support

The goal of this project is to develop unique strategies to reduce the sizes of gas exchanger devices and associated drive consoles and to provide adaptive respiratory support to ambulating ECMO patients.

• United Therapeutics, sponsor 4/21/17-12/31/24
• Sub-award to UMB: U19: NIH 2U19AI090959-12

Capital Expenditures for Cardiac Xenotransplant Study

Lung Biotechnology PBC

Bartley P. Griffith, MD, Principal Investigator (eff. 03/25/19).

Zhongun Wu, PhD, Co-Investigator

Mohammad M. Muhiuddin, MD, Co-Investigator

Genetically Engineered Pig Organ Transplantation in Baboons:  Immunological and Functional Studies

David Cooper, MD, Principal Investigator

Muhammad Mohiuddin, MD, Principal Investigator

Bartley P. Griffith, MD, Co Investigator

• United Therapeutics Corporation
• Lung Bioengineering, Inc. Pro#EVP-DEV-LTX-301

Allogeneic Recellularized Lung Orthotopic (ARLO) Research

Bartley P. Griffith, MD, Principal Investigator

Increasing Lung Transplant Availability Using Normothermic Ex-Vivo Lung Perfusion

Bartley P. Griffith, MD, PD/PI

Completed Research Support

• R01 HL 118372-01 Griffith/Wu (Co-PI)        07/05/13-03/31/2020
• R01 HL 124170-1A1 Wu/Griffith (Co-PIs)    04/20/2014-03/31/2021

First-in-Human Use of an Artificial Lung for Ambulatory Respirator Support

The goal of this project is to complete the development of an artificial pump-lung and perform the first-in-human trial of the device for ambulatory respiratory support.

Shear-Induced Hemostatic Dysfunction and Bleeding in CF-VAD Recipients

The goal of this project is to advance the understanding of device-induced hemostatic dysfunction and bleeding in heart failure patients supported with a continuous flow ventricular assist device and to use this knowledge to guide the clinical practice of device-based therapy and improve the design of ventricular assist devices.

• R01 HL 141817 Griffith/Wu (Co-PIs)                                        04/15/18-03/31/2022

Development and Pre-Clinical Trial Qualification of a Pediatric Pump-Lung System for Children

The goals of this project are to refine and complete development of a pediatric pump-lung and associated accessories and to conduct pre-clinical evaluation of readiness for manufacturing of clinical grade devices and pre-clinical testing.

Cardiac Xenotransplantation Artificial organ transplantation Artificial heart and artificial lung development Systems for pediatric heart and lung support