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Paolini, Paul J.



CMB- Professor, Ph.D., University of California, Davis,

Associate Director, Computational Science Research Center

Director, College of Sciences Office of International Programs

* Please visit my lab's website at: http://www.cardiomyocyte.sdsu.edu/ for the current information about my research, ongoing projects, and how to get in contact with members of my lab.

ppaolini@mail.sdsu.edu

paul@sdsu.edu


Dr. Paolini’s research interests are in muscle physiology, particularly cardiac muscle contractility.  Paolini currently directs two NIH student training programs and has recently taught an upper division-graduate level course about computer methods in biomedical sciences, covering bioinformatics, image analysis, data acquisition, real time experiment control and medical database management. His current research concerns signaling pathways and gene expression in the cardiac cell, physical methods of monitoring cell contractility, and use of computer models to better understand cardiac cell behavior.

 

Cardiac cell gene profiling

Dr. Paolini’s lab is investigating the mechanisms responsible for the observed beneficial effects on heart cells from a synthetic antidiabetic drug of the thiazolidinedione (TZD) family of insulin-sensitizing compounds used in the treatment of type 2 diabetes. Cell signaling pathways affected by this drug can be explored by measuring changes in expression levels of the genes controlling these pathways.  Microarray technology is used to obtain comprehensive profiling of expression and detect up-and down-regulation of genes caused by treatment with the TZD compound over time. Primary ventricular cardiomyocytes are harvested from neonatal rats and plated out on culture medium; RNA extracted and purified from these cells is then hybridized with cDNA probes on a microarray chip. Determining whether a gene is up- or down-regulated requires that its differential expression be consistent and statistically significant. Rat genes were characterized using a published functional classification scheme. The lab is examining a few genes of interest for further studies using RT-PCR, in particular, genes related to control of calcium fluxes and signaling pathways in the cardiocyte.

 

Cardiac Cell Contractile Dynamics

The laboratory continues to refine methods for assessing the contractile behavior of cardiac muscle cell preparations. Whole cell shortening and single sarcomere kinetics are measured in dissociated myocytes from adult and neonatal rat hearts, allowing the analysis of perturbations produced by altered calcium ion levels and by pharmacological agents which cause changes in excitability and contractility. Laboratory techniques in use include computerized video microscopy and calcium-sensitive fluorescence microscopy. Whole cell and sarcomere kinetics are analyzed using digital image processing methods. Information extracted in real time from sequential cell images includes sarcomere length distributions and sarcomere shortening and relaxation velocities.

 

Gene expression changes during recovery of mechanical pump-assisted failing human heart


Human heart failure is characterized by the inability of the heart to pump sufficient amount of blood to peripheral sites. Diminished pump function occurs as a consequence of the loss of viable myocardial tissue and a reduction of contractile strength of myocytes. End stage heart failure requires cardiac transplantation, but the shortage of available donor hearts makes mechanical devices (left ventricular assisted devices, or LVADs) a viable alternative. An investigation of the contractility of individual left ventricular myocytes isolated from patients before and after LVAD insertion is under way to assess myocyte alteration during the course of recovery, focusing on gene expression changes. These studies can provide an understanding of the underlying physiological basis for recovery, and can be correlated with patient clinical trials of various drug regimens.

 

Computer simulation of the contracting heart cell

A team of two graduate students in the laboratory, one trained in physics and the other in computer science, are building a detailed mathematical and graphical model of an isolated mammalian cardiac cell. The current project involves simulation of an asynchronous calcium-sensitive adult myocyte showing spontaneous rhythmic contractions. Such abnormal behaviors are thought to occur spontaneously in the aging human myocardium and can be produced readily in the laboratory using appropriately treated isolated adult heart cells. The model is being written in MatLab and OpenGL.

 

Bioinformatics

A graduate student currently completing her thesis has investigated neonatal cardiac cell gene expression pathways affected by a thiazolidinedione antidiabetic drug  on the peroxisome proliferator‑activated receptor gamma (PPARy) , a transcription factor, using genomic analysis of microarray data with a dynamic functional classification system. Regulation of specific enzymatic activities and signal transduction pathways was assessed using a meta-analysis of the published literature. Pathways studied have included apoptosis and the inflammatory response.

 

Currently in the Paolini lab:


·          Elliot Kleiman, MS in Computational Biology program
·          Camilla Dresselhuys, MS in Cell & Molecular Biology program
·          Jennifer Bennett, MS in Computational Science program
·          Melissa Quinsay, BS in Biology program
·          Lynelle Garnica Guerrero, BS in Biology program
·          Frank Gonzales, MPH program in Environmental Toxicology
·          Antonio Martinez, visiting faculty member, Simon Bolivar Univ. Caracas, Venezuela

 

Representative research publications

·          Lynelle Garnica Guerrero, Paul Paolini, Jammie Jimenez, Elliot Kleiman, Melissa Quinsay, Azhar Salim, Faramarz Valafar, and Frank Gonzales.  Gene Profiling of Cardiocytes in Response to Treatment with an Antidiabetic Drug. NIH ABRCMS Abstracts (2005)

·          Shah, R., F. Gonzales, E. Golez, D. Augustin, S. Caudillo, A. Abbott, J. Morello, P. McDonough, P. Paolini and H. Shubeita. The antidiabetic agent Rosiglitazone up-regulates SERCA2 and enhances TNFa and LPS-induced NF-kB-dependent transcription and TNF-a-induced IL-6 secretion in ventricular myocytes. Cell Physiol. Biochem. 15: 41-50 (2004)

·          Villagomez, Luis F., Paul J. Paolini and Jose Perez: Simulation of Cardiac Myocyte Contractility. NIH ABRCMS

 

Conference Abstracts (2003)

·          Reuben, H., M. Godinez, P. Paolini and E. Bejar: Analysis of contractile dynamics of adult cardiac myocytes using a computer-controlled video edge detector: effects of 5-Hydroxytryptamine. Cardiovasc. Pathobiol. 2: 149-158 (1998)

 

Education-related projects and publications

·         Alfred, Lawrence J., Cathie Atkins, Michelle Lopez, Thelma Chavez, Vernon Avila, and Paul Paolini. A science pipeline pathway for training underrepresented students in the biomedical sciences. J Women & Minorities in Science & Engineering 11, pp. 1-30 (2005)

·         Wingerd, B. and P. Paolini. Interactive Histology. CD-ROM, McGraw-Hill Publishing (1999)

·         Paolini, P. and M. Fattahipour. Heartflight! A Three Dimensional Tour through the Heart.  Software for a virtual reality examination of heart structure and function. California Affiliate, American Heart Association. (1997)

 

Academic Appointments held

1/05 – present        Director, College of Sciences Office of International Programs, San Diego State University

2/04 – present        Associate Director, Computational Sciences Research Center, San Diego State University;

8/93-1/01:              Associate Dean, College of Sciences, San Diego State University

7-91 – 6-98:           Director, Howard Hughes Medical Institute, Biology Education Initiative

5/90 - present        Scientific Director, Rees Stealy Research Foundation Laboratory, San Diego

9-84 - 1-91:           Chairman, Department of Biology, San Diego State University

9-83 - 9-85:           Founder and Director, San Diego State University Heart Institute

9-77 - 8-82:           Research Professor, Department of Physiology, University of the Pacific Dental School, San Francisco, CA

8-76-present:         Professor, Department of Biology, San Diego State University, San Diego, CA

1-79 - 9-84:           Chairman, Physiology Program, San Diego State University, CA

9-72 - 8-76:           Associate Professor, Department of BIology, San Diego State University, San Diego, CA

9-70 - 8-72:           Assistant Professor, Department of Biology, San Diego State University, San Diego, CA

9-68 - 8 70:            Assistant Professor, Division of Biological Sciences, University of Georgia, Athens, GA

 

Student and teacher training program experience:

·         MARC (Minority Access to Research Careers, NIH) program, joint SDSU-UCSD; co-Project Director (Dr. C. Atkins, PI), 1983-88;  MARC program, SDSU, 1989-present, co-PI (Dr. C. Atkins, PI).

·         REU (NSF Research Experience for Molecular Biology Undergraduates), 1989-1994; Director, 1994-6.

·         SDSU MBRS (Minority Biomedical Research Support, V. Avila, PI) Advisory Board, 1991-present .

·         TRIO Upward Bound, and Math-Science Enrichment Program (C. Park, PI), Advisory Board, 1992-present.

·         SDSU RCMS (NSF's Research Careers for Minority Scientists, Dr. M. Ring, Project Director), co-Project Director, 1992-1993; Director, 1993-1997. (program phased out nationally in 1997)

·         NIH Bridges to the Future, Director, PI, 1993 - present

·         Howard Hughes Medical Institute Biology Education Initiative, 1991-1998, Director.

·         HCOP, Health Career Opportunity Program; stand-alone program, College of Sciences, SDSU; summer program coordinator (L. Alfred, PI), 1996-8; HCOP Consortium (E. Thile, PI), Advisory Board, College of Sciences coordinator, Eisenhower Teacher Training Summer Enrichment Program, 1998-2000

·         CPEC Eisenhower award  with USI/SDUSD program CPEC Eisenhower, program Director, 2000-2002

·         Institute for K-12 Teachers;1998, Anatomy and Physiology Summer (with L. Alfred, PI)

·         NIH SEPA (Science Education Partnership Award), years 2 and 3, Program Director (with Rafaela Santa Cruz, co-Director), 1998-2001, management through Rees Stealy Research Foundation, San Diego

·         SDSU Computer Sciences, Engineering and Mathematics Scholars Program, National Science Foundation (G. Bailey, PI; P. Paolini and T. Garcia, co-PIs) 2002-2006

·         Student Support Services Program, U.S. Department of Education (Cynthia Park, PI, Cathie Atkins Kaplan and Paul Paolini, co-PIs) 2002-2005

 

Melissa Quinsay in the Lab. Melissa is an undergraduate trainee of the NIH New Interdisciplinary Workforce program at SDSU.

Melissa

 

Cardiac fibroblast prepared by Bridges students, 2005. Note geodesic dome-like actin structures.

Cardiac Fibroblast

 

2004 Bridges students at the Paolini’s; guest Marc Horowitz, Director of the NIH Undergraduate Scholarship Program, in tie; Dr. Farshid Zand, Chemistry professor at Mesa College, and Bridges summer faculty member, at left rear

2004 Bridges

 

Maureen Gibbins Paolini lecturing 2005 Bridges students. Homer Peabody, MD, Executive Director of the Rees-Stealy Research Foundation, at left.

Maureen


Note: Entrez Medline entries for a particular Author name may correspond with multiple authors with the same initials. Also, the list is limited to entries stored in the Entrez Medline Database and may not accurately reflect the true number of publications

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