Professor P D Allen

Profile

Professional Posts Held

2017-           Professor of Anaesthesia                                   University of Leeds, UK

2016-17      Anesthesiologist                                                  UC Davis Medical Center

2013-17      Adjunct Prof of Anesthesia & Pain Medicine       UC Davis

2013-17      Adjunct Professor of Molecular Biosciences       UC Davis

2012-           Professor of Anaesthesia Emeritus                    Harvard Medical School

1999-2012 Professor of Anaesthesia                                     Harvard Medical School

1986-1999 Associate Professor of Anaesthesia                   Harvard Medical School

1983-2012 Anesthesiologist                                                  Brigham and Women's Hospital

1981-1986 Assistant Professor of Anaesthesia                    Harvard Medical School

1979-1987  Consultant in Muscle Biochemistry                    Department of Anesthesia  Massachusetts General Hospital

1978-1983 Senior Associate in Anesthesia                           Brigham and Women's Hospital

1978-1981 Instructor in Anaesthesia                                     Harvard Medical School

1976-1978 Resident in Anesthesia                                       Tufts New England Medical Center Hospital       

1975-1978 Adjunct Assistant Prof of Health Sciences          Boston University

1974-1975  Post-doctoral Research Associate                     Harvard Medical School

1973-1976  Research Investigator                                        U.S. Army Research Institute   of Environmental Medicine

1972-1973 Pre-doctoral Fellow in Physiology                       University of Florida,

1969-1972  Research Fellow in Surgery                              University of Florida,

1968-1973 Associate in Surgery                                           University of Florida

1967-1968 Intern in Surgery                                                  Boston City Hospital             

Awards and Honors:

            1967                      Aid to Cancer Research Fellowship

            1971                      Conrad Jobst Foundation Award

            1972                      President's Award, Southeastern Surgical Congress

             1999                      M.S., Cum Honoris Causa, Harvard Medical School

             2001                      Vandam Lecturer, Brigham and Women's Hospital

            2004                      Academy of Anesthesia Mentors (FAER), Founding Member

            2006                      FAER Honorary Lecturer, ASA

            2007                      Distinguished Contribution Award, MHAUS

            2007                      Paul D. Allen Chair in Anesthesia Research established at  Brigham and Women’s Hospital

            2012                      Harvard Club of Australia Foundation, USA/Australia Fellowship

Research interests

The overall theme of my research for the last 40 years has focused on the regulation of calcium in striated muscle cells (skeletal and cardiac muscle). After years of research on the physiology, biochemistry and pharmacology of Malignant Hyperthermia, and attempting to determine the etiology of human heart failure, I redirected my focus from classical physiology and biochemistry to an approach that will allow studies of the functional consequences of changes in protein structure.

            Since 1991, my research has been focused on the structure-function relationships of the ryanodine receptor, one of the proteins involved in skeletal muscle E-C coupling. The central tenet of my research is that normal skeletal E-C coupling is the result of interactions among and between the proteins of the triad junction. All of these protein components of the skeletal triad act in concert during E?C coupling. Because of this, the study of the structure function relationships in or among triad proteins can only be accomplished within the context of a muscle cell. Why? The reasons for this are: first, it is only within a muscle cell that the morphology of the plasmalemma and sarcoplasmic reticulum relate properly such that E?C coupling can be reconstituted, and second, because E?C coupling is the result of a complex series of intermolecular interactions, to understand the structure function relationships of one protein or interactions between two proteins all of the rest of the components must be present. To accomplish these goals I have made genetically engineered mice and skeletal muscle cells which are deficient in the skeletal muscle ryanodine receptor, and have characterized this model so that it can be used to express mutated protein for structure function studies.

            As an expansion of the study of the structure function of the ryanodine receptor, I was the principal investigator of a 10 year long program project grant “E-C coupling-Interaction among proteins” in collaboration with 3 other investigators who are also doing research on E-C coupling. Since the termination of the PPG we continue to collaborate and continue our studies of structure function to the a1 subunit of the skeletal dihydropyridine (DHP) receptor, FKBP12, triadin and calsequestrin that are other key triadic proteins. All of these proteins have been shown to interact with Ry1R and one or more of the other proteins. Two significant milestones have permitted individual studies of how the a1 DHP?receptor or the Ry1R protein’s structure relates to function within the environmental context of the muscle cell. These are the dysgenic mouse, which has a natural mutation that makes it deficient in a1 DHP?receptor expression and the newly engineered “dyspedic” mouse that is deficient in Ry1R expression. I will use these two models new “knockouts” which have provided mice and muscle cells deficient in calsequestrin and triadin. After studying structure function relationships of these proteins in cultured muscle cells we will be able to determine the functional in vivo effects on alterations we have made in these proteins by creating “rescue” transgenic animals to “restore” lost function in a null background with mutated constructs that have been proved to be most interesting in our in vitro studies as well as using classical knock-in models done using homologous recombination in embryonic stem cells to produce new animal models.

            I set up a new and exciting line of research interest that arose from a solution developed to eliminate the technical difficulties associated with the expression of the very large Ry1R cDNA. I have had great success in using HSV1 amplicon vectors to infect dyspedic cells and get them to express RyR isoforms. Because dystrophin, the gene that is mutated in DMD children, is of a similar size to Ry1R, it may be possible to use these vectors for DMD gene therapy. Because of the problems of cytotoxicity (cell death) caused by wild type HSV1, I will use newly developed hybrid AAV/HSV1 vectors for this line of research that have no associated cytotoxicity. These vectors are also more successful in inserting themselves into the genome than HSV1 vectors and this may improve their success for gene therapy. These vectors are also more successful in inserting themselves into the genome than HSV1 vectors and this may improve their success for gene therapy. More recently this has been supplanted using CRISPR-Cas9 gene editing in both cell lines and animals to create new animal models of human disease.

Qualifications

  • 1973   PhD    Physiology  University of Florida, Gainesville, Florida
  • 1967   MD      Medicine   Boston University, Boston, Massachusetts 1967
  • 1967   BA      Medicine   Boston University, Boston, Massachusetts 1967

Professional memberships

  • 1976- American Society of Anesthesiology
  • 1976- Massachusetts Society of Anesthesiology
  • 1980- Biophysical Society
  • 1980- Cardiac Muscle Society
  • 1984-2009 Association of University Anesthesiologists
  • 1991- American Physiology Society
  • 2003- Academy of Anesthesia Mentors (FAER)

Research groups and institutes

  • Leeds Institute of Medical Research at St James's
<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://medicinehealth.leeds.ac.uk/research-opportunities">research opportunities</a> allow you to search for projects and scholarships.</p>