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Richard John Simpson

作者:时间:2019-08-14点击数:

BIOGRAPHICAL SKETCH

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NAME: Richard John Simpson

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

POSITION TITLE: Associate Professor

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

 

Napier University, Edinburgh, Scotland, UK

BSc (Hons)

05/2002

Exercise Physiology

Napier University, Edinburgh, Scotland, UK

PhD

05/2006

Immunology

Napier University, Edinburgh, Scotland, UK

Post-Doc

10/2007

Exercise Immunology

 

A.   Personal Statement

I am an Associate Professor in the department of Nutritional Sciences (College of Agriculture and Life Sciences) at the University of Arizona and hold joint appointments in Pediatrics (College of Medicine) and Immunobiology (College of Medicine). I am also part of the mentoring team for the Physiological Sciences and Cancer Biology Graduate Interdisciplinary Programs, which recruit students who are continuing in education.  My research interests are concerned with the effects of aging, stress and exercise on the immune system, and the role of adrenergic receptor signaling on immune cell redistribution and activation. Major focus areas include understanding (1) how exercise and other behavioral interventions can offset age-related decrements in the normal functioning of the immune system (immunosenescence), (2) how adrenergic receptor signaling can be used to improve cellular products for hematopoietic stem cell transplantation and immunotherapy, (3) the interplay between the immune and neuroendocrine system during high level human performance and extreme isolation (i.e. space travel), and  (3) how persistent virus infections such as cytomegalovirus (CMV) can alter the phenotype and function of T-cells and NK-cells to protect the host from certain hematological malignancies. My current research is supported by NASA, the NIH (National Cancer Institute) and industry.

 

B.   Positions and Honors

Honors

2002             University Medal Winner for best BSc Honours graduate, Napier University, Scotland

2002             Graduated with first class honours, Napier University, Scotland

2002             Prize for best oral presentation, BASES Annual Student Conference, Harrow, London, UK

2014             Promoted to the rank of Associate Professor with tenure, University of Houston

2014             Fellow of the American College of Sports Medicine (FACSM)

2017             Excellence in Research and Scholarship Award, Associate Professor Rank, University of Houston

Positions & Employment

 

INSTITUTION AND LOCATION

 

DEPARTMENT/GROUP

 

 

DATES

 

 

TITLE

 

Napier University, Edinburgh, Scotland, UK

 

Biomedicine Research Group

2006-2007

Postdoctoral Fellow

Napier University, Edinburgh, Scotland, UK

 

School of Life Sciences

2007-2008

Lecturer

University of Houston, Houston, TX, USA

Department of Health and Human Performance

2008-2014

Assistant Professor

University of Houston, Houston, TX, USA

 

Department of Health and Human Performance

2014-2017

Associate Professor

University of Texas, MD Anderson Cancer Center, Houston, TX

Behavioral Sciences

2016-present

Associate Professor (adjunct)

 

The University of Arizona

 

Nutritional Sciences/Pediatrics/

Immunobiology

 

2017-present

Associate Professor

 

 

Other Experience and Professional Memberships

2002                    Member, American College of Sports Medicine (Fellow since 2014)

2002-2008           Member, British Society for Immunology

2002-                   Member, International Society of Exercise and Immunology

2006-                   Managing Editor, Frontiers in Bioscience

2010-                   Member, American Society of Immunologists

2010                    Horizon Program - Zenith Project, Peer-Reviewer

2011-                   Member, Psycheneuroimmunology Research Society (PNIRS)

2012-2014       Guest Editor, Brain, Behavior and Immunity. Special Issue: “Exercise Immunology in Health and Disease”

2013-                   Editorial Board Member, American Journal of Lifestyle Medicine

2013                    NIAID/NIA Special Emphasis Review Panel: “Immunity and Aging”

2013-               Member, Center for Energy Balance in Cancer Prevention and Survivorship, MD Anderson Cancer Center

2014-                   Associate Editor, Exercise Immunology Reviews

2014-                   Editorial Board Member, Inflammopharmacology

2014-2019           Member, American College of Sports Medicine Research Reviews Committee

2016-                   Editorial Board Member, Brain, Behavior and Immunity

2017-                   Member, Physiological Sciences Graduate Interdisciplinary Program – University of Arizona

2017-                 Member, Cancer Biology Graduate Interdisciplinary Program – University of Arizona

2017-                   Member, Therapeutic Development Program, University of Arizona Cancer Center

2018-                   Director, Nutritional Sciences Graduate Program, University of Arizona

2019-                   Editorial Board Member, Immunity and Ageing

2019-                   Guest Editor, Frontiers in Pediatrics

 

C. Contribution to Science

 

1.    I am fascinated by the rapid response of the immune system to acute bouts of stress and exercise. The acute stress response evokes a profound immune response that augments the trafficking of cytotoxic lymphocytes between the tissues and peripheral blood. My early work showed that exercise evokes a preferential redeployment of immune cells with high cytotoxic and tissue migration potential, and that the vast majority of T-cells mobilized with stress/exercise are highly differentiated. We also showed that exercise can augment NK-cell activity against HLA-E expressing cancer target cells, due to exercise-induced increases in the proportion of NK-cells expressing activating receptors for HLA-E. I served as the primary and/or senior investigator in all of these studies:

a.    Simpson, R. J., G. D. Florida-James, C. Cosgrove, G. P. Whyte, S. Macrae, H. Pircher & K. Guy (2007) High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects. Journal of Applied Physiology, 103, 396-401.

b.    Simpson, R. J., C. Cosgrove, L. A. Ingram, G. D. Florida-James, G. P. Whyte, H. Pircher & K. Guy (2008) Senescent T-lymphocytes are mobilised into the peripheral blood compartment in young and older humans after exhaustive exercise. Brain, Behavior and Immunity, 22, 544-51.

c.    Simpson, R. J., C. Cosgrove, M.M. Chee, B. K. McFarlin, D.B. Bartlett, G. Spielmann, D.P. O’Connor, H. Pircher & P.G. Shiels (2010) Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans. Exercise Immunology Review, 16, 40-55.

d.    Bigley, A.B., Rezvani, K., Chew, C., Sekine, T., Pistillo, M., Crucian, B., Bollard, C.M. and R.J. Simpson. (2014) Acute exercise preferentially mobilizes NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Brain, Behavior and Immunity, 39, 160-171.

 

2.    Following on from my earlier descriptive work, I developed a working hypothesis to harness the acute stress response to augment T-cell therapeutics and allogeneic peripheral blood stem cell transplantation. I showed for the first time that exercise evokes a preferential mobilization of T-cells specific to a number of herpes viruses (i.e. CMV, EBV) and increases their responses to viral antigens. Low numbers of antigen-specific T-cells in blood are a major limitation for the ex vivo manufacture of cytotoxic T-cells for adoptive transfer immunotherapy. I showed that a single bout of exercise can markedly augment the manufacture of T-cells specific to both virus and tumor antigens, thus making exercise a simple and economical adjuvant to boost immune cell manufacture for adoptive transfer in cancer patients. Our most recent mechanistic work in this area has shown that exercise mobilizes and activates CD34+ stem cells, NK-cells and T-cells via signaling through the b2-adrenergic receptor, which we are now using as a therapeutic target to increase the efficacy and safety of allogeneic peripheral blood stem cell transplantation. I served as the senior investigator in all of these studies/papers:

a.    Agha NH, Baker FL, Kunz HE, Graff R, Azadan R, Dolan C, Laughlin MS, Hosing C, Markofski MM, Bond RA, Bollard CM & Simpson RJ. (2018). Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the β2-adrenergic receptor. Brain, Behavior and Immunity, 68, 66-75

b.    Graff RM, Kunz HE, Agha NH, Baker FL, Laughlin M, Bigley AB, Markofski MM, LaVoy EC, Katsanis E, Bond RA, Bollard CM, Simpson RJ. (2018) β2-adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8+ T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans. Brain, Behavior and Immunity, 74, 143-153.

c.    Simpson, R.J. A.B. Bigley, N. Agha, P.J. Hanley and C.M. Bollard (2017). Mobilizing immune cells for cancer immunotherapy. Exercise and Sports Sciences Reviews, 45, 163-172.

d.    Spielmann, G., Bollard, C.M., Kunz, H., Hanley, P.J. and R.J. Simpson. (2016). A single exercise bout enhances the ex vivo manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy. Scientific Reports, 16;6:25852

 

3.    I have a strong interest in how viral infections shape immune cell composition and function, particularly in the context of aging, stress and exercise. My NASA-funded research examines the effects of space travel, simulated microgravity analogs and extreme isolation on immune function and viral reactivation. Recently I have shown that CMV infection improves NK-cell function against tumor target cells expressing HLA-E and implicated the NK-cell activating receptor NKG2C in the response.  This preliminary work stemmed a recent R21 award focused on investigating the impact of CMV on NK-cell reconstitution and clinical outcomes in patients with multiple myeloma undergoing autologous stem cell transplantation. I served as the senior investigator/author in all of these studies/papers:

a.    Bigley, A.B., Agha, N.H., Baker, F.L., Spielmann, G., Kunz, H.E., Mylabathula, P.L., Rooney, B.V., Laughlin, M.S., Mehta, S.K., Pierson, D.L., Crucian, B.E. & R.J. Simpson (2019). NK-cell function is impaired during long-duration spaceflight. Journal of Applied Physiology, 126, 469-476.

b.    Simpson, R.J., Bigley, A.B., Spielmann, G., Kunz, H., LaVoy, E.C. & C.M. Bollard (2016). Cytomegalovirus infection and the immune response to exercise. Exercise Immunology Review, 22, 8-27.

c.    Bigley AB, Rezvani K, Shah N, Sekine T, Spielmann G, Pistillo M, Agha N, Kunz H, LaVoy ECP, Bollard CM & Simpson RJ. (2016) Latent CMV infection enhances anti-tumor cytotoxicity through accumulation of NKG2C+ NK-cells in healthy humans. Clinical and Experimental Immunology, 185, 239-251.

d.    Bigley AB, Spielmann G, Agha N, O’Connor, D.P. & R.J. Simpson. (2016) Dichotomous effects of latent CMV infection on the phenotype and functional properties of CD8+ T-cells and NK-cells. Cellular Immunology, 300, 26-32.

 

4.    I have also shown that improved physical fitness is associated with a lower age-related accumulation of ‘older’ T-cells, and have recently developed several working hypotheses as to how exercise training can facilitate health outcomes in both cancer patients and the elderly. We recently published a collaborative article outlining these frameworks in Nature Reviews Immunology and plan to test these through empirical research in the coming years.

a.    Duggal, N., Niemiro, G., Harridge, S., Simpson, R.J. & J. Lord (2019) Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity? Nature Reviews Immunology (In Press).

b.    Simpson, R.J. (2015) Fitness deficits in long-term ALL survivors. Blood, 125, 3366-3368.

c.    Simpson, R.J., Lowder, T.W., Spielmann, G., Bigley, A.B., LaVoy, E.C. and Kunz, H. (2012) Exercise and the aging immune system. Ageing Research Reviews, 11, 404-420

d.    Bigley, A.B. & R.J. Simpson (2015). NK-cells and Exercise: Implications for cancer immunotherapy and survivorship. Discovery Medicine, 19, 433-445.

 

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1nExdq2JBun5p/bibliography/48032284/public/?sort=date&direction=descending

   

D.   Research Support

Ongoing Research Support

 

NASA HRP Omnibus                          Simpson/Katsanis (Co-PI)                                                 08/01/2019-07/31/2020

“The impact of simulated microgravity on the anti-tumor properties of human NK-cells and γδ-T cells in vivo: IL-2 and zoledronic acid therapy as a potential countermeasure”

The aim of this project is to determine the effects of simulated microgravity and anti-tumor immunity in vivo using a xenotransplantation humanized mouse model with and without ZOL+IL-2 as a therapeutic countermeasure.

Role: Co-PI (with Emmanuel Katsanis)

 

NASA HRP HERO                         Simpson/Connaboy (Co-PI)                                              05/01/2019-04/30/2022

“Promoting behavioral health, cognitive, sensorimotor and immune function using guided imagery to augment exercise training in an isolated and confined spaceflight analog environment”

The aim of this project is to determine the effects of exercise with and without guided imagery on stress induced changes in behavioral health, sensorimotor and immune function.

Role: Co-PI (with Christopher Connaboy)

 

NASA NNJ13ZSA002N                 Alfano/Simpson (Co-PI)                                                  05/01/2015-04/30/2019

“Characterization of Psychological Risk Overlap with Physical Health and Associated Performance in Isolated, Confined, Extreme (ICE) Environments”

The aim of this project is to examine the impact of extreme isolation and confinement on psychological and behavioral symptoms and the role of immune/stress biomarkers to indicate early onset of potential adverse effects.

Role: Co-PI (with Candice Alfano)

 

NASA NNJ14ZSA001N-FLAGSHIP                          Simpson (PI)                                               6/01/2015-10/31/2019    

“The impact of simulated microgravity and acute radiation exposure on cytomegalovirus reactivation and host immune evasion”

This project utilizes the rotating wall vessel cell culture analog to determine the impact of simulated microgravity and acute gamma ray exposure on CMV infectivity and reactivation and its ability to evade the host immune system.

Role: PI

ORRECO (www.ORRECO.com)                              Simpson (PI)                                               01/01/2016-12/31/2018

“Immune Biomarker Profiling of Professional Athletes”

This project will attempt to identify immunological predictors of overtraining/underperformance syndrome in professional sportsmen and sportswomen.

Role: PI

NASA NNJ14ZSA001N-MIXEDTOPICS                  Simpson (PI)                                               6/01/2016-10/31/2019    

“The impact of an ISS mission on the anti-viral properties of T-cells, NK-cells, B-cells and dendritic cells”

The aim of this project is to examine the effects of 6-months space travel on the anti-viral properties of several immune cell types in astronauts.

Role: PI

R21 PAR13-146 National Institute of Health.             Simpson/Rezvani (Co-PI)                   7/01/2016-06/30/2018    

“CMV infection and NK-cell therapy for multiple myeloma”                                      

The aim of this project is to determine the relationship between CMV seropositivity, NK-cell reconstitution and complete remission rates following autologous hematopoietic stem cell transplant in patients with multiple myeloma.

Role: Co-PI (with Katy Rezvani)

Completed Research Support

 

NASA NNJ10ZSA003N                                             Simpson (PI)                                                 10/01/2011-30/09/2018

“Effects of Long-Term Exposure to Microgravity on Salivary Markers of Innate Immunity”

The aim of this project is to examine the effects of 6-months space travel on immune function and latent viral reactivation in astronauts.

Role: PI

 

Texas Institute for Rehabilitation Research (TIRR)          Thrasher (PI)                                  04/01/2011-31/03/2012

“Immune and metabolic responses to FES cycling in patients with spinal cord injury”

The goal of this project is to examine the impact of a single bout of forced electrical stimulation (FES) exercise on in vitro immune function in quadriplegics and paraplegics with a view to using FES cycling as a countermeasure against impaired immunity due to spinal cord injury.

Role: Co-I

 

NASA Human Research Program        Simpson (PI)                                                               06/01/2009-05/31/2011

“Development of a Submaximal Cycling Protocol to Identify the Ventilatory Threshold in Astronauts”

The goal of this ground-based definition study was to develop a submaximal exercise test to measure the ventilatory threshold in astronauts. Results generated from this study will be used in an applied setting to monitor changes in endurance capacity of astronauts in response to long-duration spaceflight missions.

Role: PI

 

UH GEAR                                                                          Simpson (PI)                                               8/01/2014-7/31/2017

“The effects of exercise on the generation of multi-virus specific T-cells for adoptive transfer immunotherapy: Impact of adrenergic receptors”

The aim of this project is to explore beta adrenergic receptor signaling as a pathway to enhance the generation of antigen-specific T-cells following a single bout of exercise

Role: PI  


 

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