overview

  • Research/Scholarship

    I received my Ph.D. in 1999 from the Department of Biological Sciences at Wayne State University in Detroit, MI. My dissertation research took place under the guidance of Howard R. Petty, Ph.D., and centered around understanding the biophysical interaction between IgG receptors (FcgR) and complement receptors (CR3), both located on neutrophil membranes. The results were published in two first-author articles. In addition, I examined the affect of mercury on cellular metabolism, which resulted in one first author article and one additional article. While studying the interaction between mutant and wild-type FcgRIIA and CR3, I identified one mutant phenotype as a severe defect in the ability to fuse phagosomes with lysosomes (P-L fusion).

    To extend my biophysics training and to gain expertise in molecular biology, I joined the laboratory of Alan Schreiber, M.D. in the Division of Hematology & Oncology, Department of Medicine at the Perelman School of Medicine at the University of Pennsylvania. My goal was to extend my original observations into P-L fusion and Dr. Schreiber’s laboratory was the leader in genetic engineering of FcgRs. While at Penn, I was able to identify the FcgRIIA cytoplasmic domain components required for P-L fusion and localized the functional domain within the immunoreceptor tyrosine-based activation motif (ITAM). These results were published in Blood and the Proceedings of the National Academy of Science (PNAS) and resulted in filing a patent application, which was subsequently patented and licensed to ZaBeCor Pharmaceuticals. I next initiated a project examining the function of FcgRIIA on platelets. My initial interest came from the fact that, due to the staggeringly high number of platelets in circulation, a protein (including FcgRIIA) present on platelets will have a high proportion of its total amount in the body represented by the platelet fraction. In this study, we used both human platelets, and mice expressing the human FcgRIIA on platelets, to show that platelets can bind and internalize IgG complexes. The results were published in Experimental Hematology and led to my current research interests on the non-hemostatic roles of platelets.

    I chose to join the Medical University of Ohio in September 2005 as a tenure-track Assistant Professor. Because of my expertise in FcgRIIA biology, I decided to continue studies into the biophysical interactions leading to P-L fusion. My lab was able to show that FcgRIIA requires specific membrane domains (lipid rafts) for their phagocytic activity. This is significant because knowledge of how individual FcgRs work on cell surfaces could lead to identifying new therapeutic targets for autoimmune diseases. These studies were undertaken by Joshua Vieth, my first doctoral student, and resulted in two published articles.

    During my second year at MUO/UT-HSC, I restarted my research into the non-hemostatic activities of platelets. Because of my previous expertise with FcgR and IgG-complexes, which are involved in many autoimmune diseases, I formed a collaboration with M. Bashar Kahaleh, M.D., Chief of Rheumatology Division at UTMC. This project was designed to study the activity of platelets collected from healthy volunteers and patients with systemic lupus erythematosus. At this time UT initiated the Translational Research Stimulation Awards (TRSA), and my project on “Platelet dysfunction in SLE” was selected competitively for funding. This study was an excellent project for medical students since it involved clinical experience, phlebotomy and laboratory analysis. I trained 11 medical students who worked on aspects of this project, and each of them was a co-author when their research was published. The initial SLE study was published in the American Journal of Pathology, and included seven medical students as authors.

    We have extended our observations on human platelets, to include their ability to respond to IgG-complexes by releasing select cytokines/chemokines that can stimulate inflammation. The lab has also determined that human platelets can internalize and kill bacteria, indicating they likely have a host-defense function. We are currently attempting to determine the mechanism(s) by which platelets kill bacteria, and whether they have an effect on other pathogens such as viruses. As the best way to study the functions of platelets is with in vivo systems, we created a novel transgenic mouse strain capable of conditional platelet depletion. Infection of wild-type and platelet-depleted mice intravenously with S. aureus USA300 (a major cause of human skin and soft-tissue infections) led to 100% of the platelet-depleted mice succumbing to the infection within 4 days, while over 75% of WT mice survived the infection and this work was published in the Journal of Thrombosis and Haemostasis. Based on these preliminary observations and the new research reagent (conditional platelet depletion mouse), an NIH R01 grant was awarded.

    Work we began while funded by this grant led to discovery of a bacterial product that inhibits platelet function and a US patent was issued in 2019. We received funding form iCorps@Ohio and UT Rocket Fuel Fund to develop this compound and discover the best path to market. This work continues and we established a collaboration with Isaac Schiefer, Ph.D. (UT Medicinal and Biological Chemistry) who is performing target identification using click chemistry.

    We initiated a collaboration with Heather Conti, Ph.D. (UT Biological Sciences) to investigate the role of platelets in oral Candida albicans infection. This started as a pilot project and turned into an RO1 grant awarded in January 2019. Dr. Conti and I discussed the best way to get this project funded and we determined that she should use her Early Stage Investigator (ESI) status which increased the pay line by 5-10% depending on the institute. Therefore, I took the role of Co-Investigator with 50% credit for the award. This award pays 25% of my salary, a research associate in my laboratory, and all associated costs (~$150,000 per year direct costs).

    Most recently, we identified an unmet need to understand why patients with lung cancer are at high risk of thrombosis. We began a study in collaboration with James Willey, M.D. (Department of Medicine) and we found that lung cancer patients have a high frequency of platelets aggregated with T cells. We believe these PTCAs could be used as a biomarker for lung cancer and as a predictor of thrombosis in lung cancer patients. The initial publication is currently submitted and we are developing this into a grant application for RO1 and DoD mechanisms.

    We also have a current collaboration including one published article and one submitted manuscript with Francis Pizza (UT Kinesiology) examining the role of inflammatory cell infiltration during muscle repair. A second collaboration is with Eda Yildirim-Ayan (UT Engineering) studying the effect on macrophage polarization of mechanical loading. This collaboration has produced one review article in press and a R15 grant proposal submitted in June 2019. An NIH R21 proposal is expected to be submitted in February 2020.

    In summary, my research program since coming to MUO/UT-HSC has resulted in six peer-reviewed grants (four national, two local) and 18 published articles, of which I am senior author on twelve. In total, I have published 30 peer-reviewed articles, of which I am first author on eight and senior author on twelve. Since being promoted to Associate Professor, I have seven publications and I am listed as senior author on five. I also have three manuscript submitted and four others in preparation as senior author, and two as a collaborator and co-author.

    Teaching

    I have been involved in teaching since I was an undergraduate at the University of Charleston in West Virginia, where I was approached in my junior year to help teach the Anatomy and Physiology lab. During graduate school at Wayne State, I was required to teach as part of the financial package to support my education. I had wonderful experiences teaching Embryology to senior undergraduates and post-baccalaureates, and then spent three years teaching laboratory sections of Anatomy & Physiology to undergraduate health science students. At the University of Pennsylvania I sought out an instructor position in the College of Lifelong Learning where I taught evening courses in Advanced Cell Biology in the winter and Human Genetics in the fall. I thoroughly enjoyed this experience and it set the foundation for a love of teaching that still drives me today.

    Since arriving in September 2005, I have embraced teaching and interacting with students in any way I can. On the medical student side, I give 6-7 lectures in Block 4 (Immunity and Infection)/Thread 1 (Immunity/Infectious Diseases), and lead laboratory and POPS sessions for the second-year class (now first year class). I taught Clinical Decision Making (CDM) course for several years. I developed a new elective for fourth-year medical students (BSCI 780 – Independent study in rheumatic diseases), which I have offered since 2010. I have enrolled nine students who performed bench research, chart reviews, or meta-analyses and delivered summarized documents exhibiting their hypothesis, methods, results and conclusions.

    For graduate students, I provide didactic lectures in three courses and serve as moderator in two additional courses. I was the initial course director for Advanced Immunology, and also Current Topics in IIT, until 2014.

    From an evaluation standpoint, my lectures continually rank in the 3.5/4.0 and 4.4/5.0. At the conclusion of each lecture, I review statistics of Poll Everywhere questions so I can determine where students are getting the message and where I need to improve. I also read every comment from students and review/update lectures as trends appear. Therefore, I continually look to improve the course and my teaching based on student feedback and performance.

    Finally, my role as a student mentor in the laboratory has helped three graduate degree recipients, four post-doctoral fellows, 20 medical students, and two high school students. Of the degree recipients, my first Ph.D. student, Dr. Joshua Vieth is director of immune monitoring at the New Jersey Cancer Institute, my MSBS student Dr. Elizabeth Beil is an Emergency Medicine physician at Maine Medical Center. My second Ph.D. student, Claire Meikle is currently completing the M.D. portion of her M.D., Ph.D. combined degree.

    In recognition of my teaching efforts, I received the Dean’s Award for Teaching Excellence – Junior Faculty Category in 2008. I was also nominated for outstanding mentor award in the college of medicine and life sciences and the college of graduate studies.

    Service

    On the national level, am an associate editor at Frontiers in Cell and Developmental Biology. I continue to serve as an ad hoc reviewer for >14 immunology and cell biology journals. I have reviewed grant proposals on an ad hoc basis for the Center for Scientific Review (NIH), Arthritis Foundation, American Heart Association, the Polish Academy of Science, and Medical Research Council (UK). I served as a permanent member of an American Heart Association study section (2008-2011).

    At the institutional level, I currently serve (since July 2019) as Associate Dean for Student Affairs & Admissions where I oversee all aspects of Student Affairs and Admissions in the MD program. The office of student affairs is responsible for career advising, leadership and professional development and bridge ceremonies (orientation, commencement, match day). I have re-organized the office to optimize use of expertise. This includes me overseeing the preclinical students from matriculation through the first board exam (USMLE Step 1). Once students begin clinical training, I have charged an Assistant Dean who is also a practicing pediatrician to oversee their progress. I have also implemented organizational charts for our office so students know who they should contact for any issue which they may need assistance. I oversee MD student resident application (National Resident Matching Program) and generate the medical student performance evaluation (MSPE – formerly the Dean’s letter) for each graduating M4 student. My task as the Associate Dean of Admissions is to provide leadership to the process of filling a class of 175 MD students each year from approximately 5000 applicants. I serve as a co-chair of the admissions committee and handle issues related to office staffing, regulatory approval and student tracking. A major responsibility of my position as Associate Dean for Student Affairs and Admissions is accreditation. The Office of Student Affairs and the Office of Admissions account for nearly 30% of the accreditation through the liaison committee for medical education (LCME) which will review our MD program in April 2021.

    My previous administration position was Assistant Dean for Student Affairs where I oversaw the preclinical students and also implemented a reworked medical student research program that includes formal application, committee review, and tracking of student progress and evaluation. These changes will allow us to develop NIH-funded programs to support the program in the near future.

    Additionally, I have served on a number of committees on the HSC. For the Medical School, I have served on the Medical Student Promotions Committee and the Student Conduct and Ethics Committee (2006-2017). I served as Chair of the Medical Student Promotions Committee from 2014-2017. I have also served on the Medical Student Research Committee (2007 – present, currently as Chair) and MD/PhD Committee (2008 – 2010). I participated in the 2012 LCME Self Study by serving as a member of Workgroup Section 3: Medical Student Issues, and on the LCME Self Study Steering Committee. I spent several years interviewing medical school applicants, averaging about 25 per year. For Graduate Studies, I was a member of the Biomedical Sciences Graduate Program Admissions Committee from 2007 – 2009 and served as a faculty mentor for the Council of Biomedical Graduate Students (CBGS) with Randall Ruch from 2007-2014. As of 2019, I now serve as Chair of the Academic Progress Committee, the Dean’s Committee on Libraries, the Criminal History Review Committee, the Graduation Committee, the Medical Student Research Committee, and I serve as a member on the Executive Curriculum Committee.  

    At the department level, I served on the Faculty Recruitment Committee from 2006 – 2009, which successfully recruited three faculty members (S. Stepkowski, V. Ferreira, J. Huntley). I currently Chair the faculty recruitment committee seeking to recruit two junior or mid-career faculty members. I worked closely with Dr. Akira Takashima, Director, and served as the Co-director of the Ohio Center for Innovative Immunosuppressive Therapeutics (OCIIT), which received a grant from the Ohio Department of Development to support a joint interaction between our department and the department of Dermatology at Case Western Medical School. My efforts led to organizing the first OCIIT Research Forum in 2008 – 2009 when we held joint research meetings in Sandusky, OH and Columbus, OH. In an attempt to bring the most cutting edge technology to the HSC, I organized the Science and Technology Expos (2007 – 2009) where scientific equipment companies presented their newest technologies at a two-day event in the Health Education Building (2007, 2008) and then at the Dana Center (2009).

    On the community level, I served as the chairperson of the Gala committee for the NW Ohio chapter of the Arthritis Foundation from (2008 – 2009). In this role, I worked with volunteers and the regional director to organize and host the annual fundraiser, a black-tie casino night. Over the two years, these events raised over $50,000 to support the Arthritis Foundation missions in research and community care. From 2008 – 2009 I also spoke at two well-attended public presentations on recent research updates to the community. Additionally, I volunteered with the local chapter of the Lupus Foundation where I presented short seminars and served as a moderator for discussion about new research and therapeutics in lupus. I have made brief presentations in my children’s elementary school classrooms on basic scientific ideas and hosted two Weird Science Days in association with the Mothers Center of Greater Toledo where I hosted more than 20 children at my home and performed many science experiments to raise awareness and excitement in the sciences. I presented to McCord Junior High School 6th grade science class about bacteria, immunology, and cell biology. I also presented to McCord Junior High School 8th grade class about careers in science. Most recently, I participated in Skype A Scientist with a 12th grade science class in Los Angeles. The discussion was directed at describing our science, what it’s like being a first generation college graduate, my path to becoming a scientist, and potential career pathways.

    Aside from science, I have coached my children’s soccer, baseball and basketball teams and work with groups of children on learning golf skills and etiquette. I have been a member of the U-Tee golf league (formerly MCO Golf League) since 2006 and served as its president for three years (2008 – 2011) and as league secretary for six years (2012 – 2018).

selected publications

full name

  • Randall G Worth

visualizations

Cumulative publications in Scholars@UToledo