This year’s USF Health Research Day set new records as more participants than ever filled the USF Tampa campus Marshall Student Center on March 3 to showcase the best of their scientific work.

The 33^rd USF Health Research Day included 457 research poster presentations by students, postdocs, residents, faculty, and staff across all health disciplines. Research Day is the largest research-oriented event of its kind at USF and remains the largest celebration of health sciences research collaboration across all four USF Health colleges (medicine, nursing, public health and pharmacy) as well as with colleagues in other USF colleges, including social work and engineering.

From left, Dr. Charles Lockwood, Dr. Kim Orth, Rhea Law, and Dr. Steve Liggett.

Research Day kicked off with the Annual Roy H. Behnke, MD, Distinguished Lectureship featuring speaker Kim Orth, PhD, professor of Molecular Biology and Biochemistry at University of Texas Southwestern Medical Center and an investigator at the Howard Hughes Medical Institute, at UT Southwestern Medical Center.

Dr. Orth’s presentation was titled “Black Spot, Black Death, Black Pearl: Tales of Bacterial Effectors” – click here for more about Dr. Orth and her work.

Dr. Kim Orth.

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Tampa General Hospital, the primary teaching hospital for USF Health Morsani College of Medicine, was the presenting sponsor for USF Health Research Day 2023.

Following Dr. Orth’s presentation was the judging of work. Judges reviewed the posters that lined the Marshall Center Ballroom, asking the students for more detail and clarifications about their research projects. Presentations ranged from pilot, preliminary, empirical and case studies to system reviews and reviews of literature or charts.

Following the 13^th Annual Joseph Krzanowski Invited Oral Presenters by select students representing medicine, nursing, public health, and pharmacy, Research Day culminated with an Awards Ceremony in the Oval Theatre announcing the winners in 29 competitive categories – including 18 monetary awards totaling $8,600.

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For the list of Research Day 2023 award winners, click here.

For the list of Research Day judges and sponsors, click here.

More photos

Photos by Freddie Coleman, video by Allison Long, USF Health Communications

Leaders from USF Health and the Global Virus Network (GVN) recently gathered on the University of South Florida campus in north Tampa to sign the final documents making it official that USF Health serves as GVN’s Southeast United States Regional Headquarters.

USF Health and GVN announced nearly two years ago that USF Health earned the designation, but COVID-19 delayed the official signing until this year. The signing took place at the USF Lifsey House Feb 27, 2023, and marks the advancement of the collaborative relationship among the two organizations.

From left, Dr. Charles Lockwood, Pres. Rhea Law, Mathew Evins, and Dr. Christian Brechot.

“What we are signing together today marks a first, that USF is the first regional headquarters to be created with GVN,” said Christian Bréchot, MD, PhD, president of GVN; associate vice president for International Partnerships and Innovation at USF; director of the USF Microbiomes Institute, and professor in the Division of Infectious Disease, Department of Internal Medicine at the USF Health Morsani College of Medicine. “This headquarters at USF will allow GVN to expand its outreach into Florida with USF’s academic, research and medical activities and expertise, including USF’s international activities. In turn, GVN will provide to USF increased visibility and critical mass across the globe in the field of virology.”

“We are so excited to be the headquarters for the Global Virus Network,” said USF President Rhea Law. “This is an initiative in which we can have enhanced collaborations that focus on huge issues affecting our world today. We can make a difference. Thank you so much for all you’ve done. We are looking forward to our collaboration and to our next steps in opportunities to change the world.”

“We are very grateful to be the Southeast Regional Headquarters and this is a significant stepping stone to where we are headed in virology,” said Charles J. Lockwood, MD, executive vice president of USF Health and dean of the USF Health Morsani College of Medicine. “One of the key elements of putting this all together is Christian Bréchot. He has been such an incredible resource, for recruitment of virologists, addressing microbiome, and strengthening many of our programs. It has been a joy to see this collaboration develop and grow. So now, the sky is the limit with this great team in place.”

“On behalf of Bob Gallo, the Board of Directors, and the leadership of the Global Virus Network, I would like to express our most profound appreciation to the University of South Florida for its invaluable and instrumental partnership,” Mathew Evins, executive chair and treasurer of the GVN Board of Directors and chair of Evins Communications, Ltd. “I’ve been involved with GVN from the beginning and I cannot think of a situation where I have been more proud. This is a very significant step for us because the key to the successes of GVN in the future are the kind of partnerships we have with the University of South Florida. This for us is not an incremental step; it is an exponential step. I could not be more grateful for your support, your encouragement, and your partnership.”

GVN encompasses the world’s foremost virologists from 71 centers of excellence and 9 affiliates in 40 nations – all working to prevent illness and death from viral diseases posing threats to humanity. Bridging academia, government and industry, the coalition is internationally recognized as an authority and resource for identifying, investigating, interpreting, explaining, controlling, and suppressing viral diseases.

USF Health was the first regional headquarters named by GVN to provide organizational and leadership support to GVN’s Global Headquarters in Baltimore, Md. In that capacity, USF Health will help strengthen GVN’s initial research response to emerging and re-emerging infectious diseases, such as COVID-19, and its collaborative efforts to plan for, and defend against, future epidemics and pandemics.

Since announcing USF Health’s designation as the GVN Southeast United States Regional Headquarters, the two organization have launched several programs, including the Global Health Conversation Series with USF Health International that hosted a recent webinar featuring Rachel Roper, MS, PhD, who spoke on Monkeypox virus, vaccines and virulence; Dr. Bréchot’s Health and Care Blog that provides updates on novel insights into the COVID-19 pandemic; One Health Codeathon, an effort between GVN and the USF Genomics Program that provides students the opportunity to learn how to harness data sciences against pandemics; and submission of several joint grant applications, including to the National Science Foundation and the National Institutes of Health.

The GVN Southeast U.S. Regional Headquarters based at USF Health will encompass the four health sciences colleges of the university: the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, and the USF Health Taneja College of Pharmacy. USF Health is an integral part of USF, a high-impact global research university dedicated to student success. Over the past 10 years, no other public university in the country has risen faster in U.S. News and World Report’s national university rankings than USF.

The appearance of COVID-19 has transformed society almost beyond recognition, with lasting implications for health care, the economy and our social and psychological well-being. Together we can, and we must, be better prepared to meet the challenges of the next emerging virus.”

In addition to their leadership roles at GVN Global Headquarters in Baltimore, Md., Dr. Bréchot and GVN Vice President Linman Li of the USF Health Division of Infectious Disease and International Medicine will lead the new GVN Southeast U.S. Regional Headquarters and focus on regional efforts to expand government and other research funding, as well as research and training initiatives. The regional headquarters designation will enable USF Health scientists to partner with GVN experts worldwide to share ideas and research, to translate research into practical applications, to improve diagnostics and therapies, and to develop vaccines.

GVN members collaborate on science-driven, independent research in many areas, including immunology and vaccines, antiviral drug therapy, virus-host interaction, diagnostic virology and epidemiology, morphogenesis and structural biology, emerging and re-emerging viruses, viruses as biotechnological tools, and trending topics in virology. They also train the next generation of virologists to combat the epidemics of the future.

Video by Allison Long, photos by Freddie Coleman, USF Health Communications

The invention that was shared with the world: Experts came together quickly in early 2020 to create a 3D-printed nasopharyngeal swab. Today, more than 100 million swabs have been produced across the globe using this USF-patented design, and the U.S. Patent and Trademark Office is honoring the USF Health team Feb. 16, 2023.

The University of South Florida (USF) has been awarded the Patents for Humanity award by the U.S. Patent and Trademark Office (USPTO) for its patent of the 3D-printed nasopharyngeal (NP) swab, created in the early part of the pandemic as a solution to the disrupted commercial production of standard flocked NP swabs critical in diagnostic testing for COVID-19.

USF is among an exclusive group of winners receiving this year’s Patents for Humanity awards, being named alongside the National Institute of Allergy and Infectious Diseases of the NIH, Regeneron Pharmaceuticals, Gilead Sciences Inc., and Caron Products. All will be honored by the USPTO at an awards ceremony on February 16, 2023.

USF is earning this recognition for its innovative solution to the commercial NP swab shortage. Due to the urgent need worldwide, the 3D-printed NP swab team decided to forgo monetization of their invention and provided the design files and clinical data at no cost to hospitals, clinics and licensed medical device companies around the world as long as the swabs were produced for their own use.

Over the span of one week in March 2020, teams from USF Health, Northwell Health, Tampa General Hospital, and Formlabs worked together to develop a 3D printed swab prototype using Formlabs’ 3D printers and biocompatible (not harmful), autoclavable materials (able to withstand elevated temperature and pressure of an autoclave). The prototypes were then benchmarked against standard flocked swabs for viral sample retention in the laboratory and tested for patient safety and comfort by USF Health Morsani College of Medicine Department of Internal Medicine researchers. After passing these tests, the teams initiated a multisite clinical trial at dozens of hospital sites across the United States, including Tampa General Hospital, Northwell Health in New Hyde Park, New York, and Thomas Jefferson University Hospital in Philadelphia, comparing performance of the 3D-printed nasopharyngeal swabs with flocked swabs.

From that point on, the USF/Northwell design was shared with hospitals, health systems, the military, and clinics around the globe. To date, the USF-patented design for the 3D-printed nasopharyngeal swab has been shared with institutions in more than 60 countries that have produced more than 100 million swabs.

“I am so proud of how our USF Health team stepped forward to combine their expertise and innovation with the teams from Tampa General Hospital, Formlabs and Northwell Health to help save lives around the world,” said Charles J. Lockwood, MD, MHCM, executive vice president for USF Health and dean of the USF Health Morsani College of Medicine, and executive vice president and chief academic officer at Tampa General Hospital. “This recognition by the U.S. Patent and Trademark Office validates both the tremendous power of academic medicine, especially during a crisis, and the values and commitment these teams have for contributing to the greater good.”

“Our goal from the start was to help as many people as possible, as fast and safely as possible,” said Summer Decker, PhD, professor in the USF Health Morsani College of Medicine, and director for 3D Clinical Applications in USF Health’s Department of Radiology, who led the 3D printed NP swab team. “In order to do that, we assembled a team of experts in our fields and worked together toward a real-world solution. We then made our files public so that any hospital, clinic or health system could print them for their own facilities and get them to the frontline of COVID-19 testing in patients. Only when you know what you are truly facing, in this case COVID-19, can you actually fight it. This swab was a critical, missing component of the global medical community’s ability to do just that. We are very humbled by this recognition by the U.S. Patent and Trademark Office for our efforts and very grateful for this incredible opportunity to help not just USF Health and Tampa General Hospital, but also other hospitals and medical centers throughout the world.”

“COVID-19 demanded innovation and collaboration, not only from those on the front lines but across industries,” said Todd Goldstein, PhD, director of 3D Design and Innovation at Northwell Health. “It’s an honor to receive this recognition from the U.S. Patent and Trademark Office and we hope that our 3D printed nasal swab design helped alleviate burden during the height of the pandemic and showed what cooperation, even in times of crisis, can achieve.”

“We were proud to unite with USF Health, Formlabs and Northwell Health to work quickly and collaboratively to save lives during the height of COVID-19 when swabs were in short supply and in such high demand,” said John Couris, president and CEO of Tampa General Hospital. “This recognition is a true testament to not only the power of academic medicine, but the hard work, sacrifice, innovative spirit and perseverance of our clinical teams and their ability to act quickly and think strategically. We are thankful for the partnerships we developed with other health leaders to find innovative and cost-effective solutions to protect the health of our region and beyond.”

“With quick thinking and action from USF Health, the global shortage of traditional nasopharyngeal swabs was minimized with an entirely 3D printable design that could be easily printed in health care facilities around the world,” said Gaurav Manchanda, director of Medical Market Development at Formlabs. “We were honored to help in this effort and pleased to see the reliability, scalability, and accessibility of our 3D printing solutions put into action. By combining the centralized quality, regulatory, and medical manufacturing expertise at Formlabs with a decentralized production network of global medical customers, local health institutions were able to print and use millions of swabs needed during the shortage. Formlabs is proud to be recognized alongside USF Health, Northwell Health, and Tampa General Hospital in the USPTO Patents for Humanity COVID-19 category.”

The team that created the USF-patented 3D printed nasal swab, from left, Jonathan Ford, Kami Kim, John Sinnott, Summer Decker, Todd Goldstein, and Michael Teng. Not pictured is Todd Hazelton.

— Video and photos by Allison Long, USF Health Communications

Faculty and clinical staff from both USF Health and Tampa General Hospital learned the nuances and best practices of ECMO (extracorporeal membrane oxygenation) at a special course held on the TGH campus last month.

The recent ECMO course provided the newest information associated with the life-saving procedure and was led by Kapil Patel, MD, associate professor and director of the USF Health Center for Advanced Lung Disease in the USF Health Morsani College of Medicine and director of the TGH Lung Transplant Program, and M Raheel Qureshi, MD, assistant professor and associate medical director of the ECMO program in the Division of Pulmonary, Critical Care and Sleep Medicine in the USF Health Morsani College of Medicine, and associate director of the Lung Transplant Program at Tampa General Hospital.

ECMO is used in critical care situations, when the heart and lungs need help as the patient heals. In ECMO, blood is pumped outside of the body to a heart-lung machine that removes carbon dioxide and sends oxygen-filled blood back to tissues in the body. Blood flows from the right side of the heart to the membrane oxygenator in the heart-lung machine, and then is rewarmed and sent back to the body.

This method allows the blood to “bypass” the heart and lungs, allowing these organs to rest and heal.

Many providers and hospitals around the world saw an uptick in patients needing ECMO as part of the COVID-19 care they received in intensive care units. Now, as COVID continues to subside, expanding training on ECMO better prepares health care teams and hospitals if another surge of COVID – or other related viruses – take hold.

Published studies show that hospitals and facilities with more ECMO experience have better outcomes. ECMO is complex in its execution, requiring trained staff and specialist equipment, making the USF Health/TGH training course a critical part of preparation for another COVID surge or pandemic.

Health care providers across the country learned very quickly during the pandemic that ECMO could save lives and it was used largely in patients with COVID-19 with acute respiratory distress syndrome (ARDS). Published studies show importance of carefully selecting patients for a critical care treatment requiring intense staffing, specialized equipment and advanced expertise.

The USF Health/TGH training sessions mean that more providers are prepared to treat patients sooner with ECMO and improve outcomes.

Photos by Freddie Coleman and Ryan Rossy, USF Health Communications

USF research teams led by Dr. Yu Chen and Dr. Xingmin Sun describe ways to control the No. 1 hospital-acquired bacterial infection in a paper published in the journal Nature Communications.

The ironic joke goes that if you want to get sick, stay in a hospital. That’s because hospitals can harbor germs that take advantage of a patient’s weakened state, complicating the illness that brought them there in the first place.

But health officials have an arsenal to keep people safe, including cephalosporins, strong antibiotics that fight bacteria such as staphylococcus and streptococcus. Cephalosporins are often used against skin, soft tissue and surgery related infections.

Dr. Yu Chen

However, treatment with β-lactam antibiotics – particularly cephalosporins – is a major risk factor for the virulent Clostridioides difficile infection (CDI), which attacks the large intestine and can cause diarrhea and life-threatening colitis.

These complications are explained in a recent paper published in the journal Nature Communications by teams that includes senior author Dr. Yu Chen, professor in the Department of Molecular Medicine in the USF Health Morsani College of Medicine, and co-corresponding author Dr. Xingmin Sun, associate professor in the Department of Molecular Medicine in the Morsani College of Medicine. Several other USF research teams, led by Rays Jiang, PhD, Prahathees Eswara, PhD, and Ioannis Gelis, PhD, also contributed to the study.

“When you give a person an antibiotic to treat a disease, one of the consequences is the antibiotic can wipe out a lot of the good bacteria in the gut,’’ Dr. Chen said. “But in this case, C. difficile is resistant to cephalosporins, so it creates a high-risk factor. And if people are under prolonged antibiotic treatment, they are at an even higher risk for CDI.’’

Cephalosporin resistance in CDI is well documented, but the underlying mechanism has, until this point, remained unclear. The USF Health team used a combination of experimental techniques to characterize the molecular basis of cephalosporin resistance in CDI, which is the No. 1 hospital-acquired bacterial infection in the United States, according to the Centers for Disease Control and Prevention.

Initially, antibiotics are administered for an unrelated infection or prophylaxis, causing the gut flora diversity to diminish. Without competition from the good bacteria in the large intestine, CDI can easily proliferate, secreting toxins that cause cell death.

“The primary risk factor for CDI are broad-spectrum antibiotics, specifically those with weak activity against C. difficile and strong activity against other gut bacteria,’’ the authors state.

These broad-spectrum antibiotics irreversibly inhibit a bacterium’s penicillin-binding proteins (PBPs), which are enzymes that assemble in the bacterial cell wall. These proteins are critical not only for the growth of C. difficile, but also to produce its spores, which are resistant to harsh environmental conditions and contribute to the high recurrent rates of CDI. The challenge for researchers is that, prior to the Nature Communications report, there was little information about the PBPs of C. difficile.

As a common hospital-acquired infection, the pathogenesis of CDI is well-understood. It causes about 500,000 infections each year in the United States, and one in about 10 people over 65 with the infection die within a month, according to the CDC.

“We want to know more about C. difficile resistance so it (data) can be used to create new therapies for the future,’’ Chen said. “This research will help us understand more about certain drugs that are risks factors for infection.’’

The researchers emphasized two key findings in the journal report. First, by elucidating the three-dimensional structures of key PBPs from C. difficile and how they interact with beta-lactam antibiotics, the USF Health teams showed that cephalosporins do not have strong inhibitory activity against the PBPs essential for C. difficile growth and are thus unable to kill the bacterium.

Second, they also found that many of these proteins require zinc to be functional, partly explaining why dietary zinc is also a risk factor for CDI. Furthermore, the results can be used to develop new inhibitors of these PBPs to kill C. difficile and eliminate its spores. Such compounds can be developed into new antibiotics to treat CDI.

CDI can affect anyone, and symptoms often are painful and life threatening. Risk factors include:

• Being 65 or older
• Recent stay at a hospital or nursing home
• A weakened immune system, such as people with HIV/AIDS, cancer, or organ transplant patients taking immunosuppressive drugs
• Previous infection with CDI or known exposure to the germs

For more information, visit https://www.cdc.gov/cdiff/risk.html

The journal Nature Communications is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical and Earth sciences. Papers published by the journal aim to represent important advances of significance to specialists within each field.

Story by Kurt Loft

The USF Health Morsani College of Medicine Academy of Distinguished Educators class of 2022 (Left to right): Eduardo Gonzalez, MD, FAAFP; Andreas Seyfang, PhD; John Armstrong, MD, FACS; Marzenna Wiranowska, PhD, MS; Susan Pross, PhD.

The USF Health Morsani College of Medicine (MCOM) recently celebrated the newest members of the Academy of Distinguished Educators during a small induction ceremony Sept. 20.

Class of 2022 Inductees:

• John Armstrong, MD
• Eduardo Gonzalez, MD, FAAFP
• Susan Pross, PhD
• Andreas Seyfang, PhD
• Marzenna Wiranowska, PhD, MS

“To us falls the high privilege and great responsibility of training the generation of doctors.  If we fail to do our job to perfection, people die needlessly.  Too often this simple truth is forgotten, but each of you never forget.” said Charles J. Lockwood, MD, MHCM, USF Health executive vice president and MCOM dean. All of you are a testament to why MCOM continues to thrive and why our reputation across the nation continues to rise.”

The program was developed as a collaborative effort by MCOM’s Department of Medical Education, Faculty Council, and Office of Faculty Affairs to enhance the practice, quality and scholarship of teaching and learning at the medical school through educational service, consultation and research.   The program honors exemplary educators of all medical students, physicians, physician assistants, physical therapists, athletic trainers and scientists within the faculty by awarding the prestigious title of Distinguished Educator.

Nominees must hold an active appointment at MCOM for at least two years and hold the minimum title of associate professor.  Nominees must have made exceptional contributions to the education mission in one or more of the following ways:

• Research in education.
• Innovations and scholarly approaches in curriculum development, instructional design, or assessment of student learning.
• Mentoring and development of faculty as educators or educational researchers.
• Individual learner mentoring and development.
• Leadership in education.

About the Inductees:

John Armstrong, MD, FACS.

John Armstrong, MD, FACS  is a nationally recognized surgeon and USF Health professor who has held multiple positions within USF Health and the Florida government.  He served as chief medical officer of the Center for Advanced Medical Learning and Simulation (CAMLS), surgical director of the USF Health American Colleges of Surgeons Accredited Education Institute and professor in the MCOM Department of Surgery.  He also served as Surgeon General and Secretary of Health under former Governor Rick Scott from 2012 to 2016.

Eduardo Gonzalez, MD, FAAFP.

Eduardo Gonzalez MD, FAAFP, joined USF Health in 1994.  He  serves as a professor and director in the MCOM Department of Family Medicine, professor in the Taneja College of Pharmacy Department of Pharmacy Practice.  He is co-medical director of the USF Health BRIDGE Clinic, a free student-run clinic that serves uninsured adults from underserved communities.  In 2019, Dr. Gonzalez was named Physician of the Year by the American Academy of Family Physicians.  He is also a two-time USF alum having completed his undergraduate degree in 1987, and medical school in 1991.

Susan Pross, PhD.

Susan Pross, PhD has been part of the Morsani College of Medicine since 1975.  She is a professor in the MCOM Department of Molecular Medicine and director of the MCOM Office of Research Innovation and Scholar Endeavors Scholarly Concentrations Program, where she helps to develop and assess elective opportunities for student scholarship.   She is a trained immunologist and microbiologist  with research interests in allergy, immunology, and infectious disease.

Andreas Seyfang, PhD.

Andreas Seyfang, PhD is an expert in medical microbiology and parasitology.  He holds several professor positions throughout the USF Health colleges to include the Morsani College of Medicine, College of Public Health and School of Physical Therapy and Rehabilitation Sciences.  He’s earned multiple outstanding instructor and teaching awards that are voted on by students.  He is the director of the Seyfang laboratory that focuses on membrane permeases as target for drug delivery, and cytochrome b5 reductase as enzymatic drug target in opportunistic microbial pathogens including protozoan parasites and nosocomial and neuro-pathogenic fungi.

Marzenna Wiranowska, PhD, MS.

Marzenna Wiranowska, PhD, MS is an international expert in microbiology and immunology.  She joined the USF Health staff in 1982 where she started as a research associate in the Immunopharmacology Program at MCOM and currently serves as an associate professor in the Department of Pathology and Cell Biology.  She leads the Medical Humanities elective of the Scholarly Concentrations Program.  Dr. Wiranowska has earned many awards as an educator of medical students including the Most Outstanding Pre-Clinical Professor Award voted on by the MCOM class of 2019.

Story by Freddie Coleman.  Photos by Ryan Rossy

USF Health doctors are among the best and listed as such in the Top Doctor® list by Castle Connolly.

The list, released earlier this year, includes over 400 local physicians among 55 medical specialties – 82 of them are with USF Health.

USF Health Neurologist Dr. Theresa Zesiewicz.

For more than 25 years, Castle Connolly has conducted the survey that provides the Top Doctors list.

The annual survey involves nominations from peer physicians, who are asked “Where would you go if you needed care?” The process is anonymous and confidential, and doctors cannot nominate themselves. The resulting list, based on merit and inclusion cannot be bought, provides a collection of trusted resources for quality health care.

On this year’s list, 82 physicians on the list are with USF Health. The following list is of USF Health faculty physicians currently practicing medicine within nearly three dozen clinical sites, specialty care centers and affiliated hospitals throughout the region.

Allergy & Immunulogy
Mark C Glaum, MD, PhD
Richard F Lockey, MD
Mandel R Sher, MD
Jolan E Walter, MD/PhD

Cardiac Electrophysiology
Bengt Herweg, MD

Child Neurology
Sagarika Nallu, MD

Colon & Rectal Surgery
Jorge E Marcet, MD
Jaime E Sanchez, MD

Dermatology
Basil S Cherpelis, MD
Nishit S Patel, MD

Endocrinology, Diabetes & Metabolism
Madeline Candelario-Cosme, MD
Yevgeniya Kushchayeva, MD

Family Medicine
Eric E Coris, MD
Eduardo C Gonzalez, MD
Kira K Zwygart, MD

Gasterenterology
Patrick G Brady, MD
John W Jacobs Jr, MD
Jay J Mamel, MD
Joel E Richter, MD
Pushpak Taunk, MD

Gynecology Oncology
Diana Peta-Gay English, MD
Thomas J Rutherford, MD, PhD

Infectious Disease
Sally Fathi Alrabaa, MD
Beata C Casanas, DO
Ambika Eranki, MD
Charurut Somboonwit, MD

Internal Medicine
Nathan A Brinn, MD
Denise K Edwards, MD
Lucy Guerra, MD
John D McCormick, MD
Hugo J Narvarte, MD
Kevin E O’Brien, MD

Interventional Cardiology
Fadi Matar, MD

Maternal & Fetal Medicine
Jan M Lanouette, MD
Charles J Lockwood, MD
Judette M Louis, MD
Stephanie Teresa Ros, MD

Neurological Surgery
Thomas B Freeman, MD
Donald A Smith, MD
Harry R Van Loveren, MD

Neurology
William Scott Burgin, MD
Rossitza I Chichkova, MD
Clifton Gooch, MD
Robert A Hauser, MD
Juan R Sanchez-Ramos, MD
Tuan H Vu, MD
Theresa A Zesiewicz, MD

Obstetrics & Gynecology
Shelly W Holmstrom, MD
Catherine M Lynch, MD
Dawn Palaszewski, MD
Odalis Sijin, MD

Ophthalmology
Ramesh S Ayyala, MD
Mitchell Drucker, MD
Lewis Groden, MD

Orthopaedic Surgery
Roy W Sanders, MD

Otolaryngology
Mark H Tabor, MD

Pediatric Endocrinology
Ellen Verena Jorgensen, MD
Henry Rodriguez, MD
Dorothy Shulman, MD

Pediatric Infectious Disease
Carina A Rodriguez, MD

Pediatric Nephrology
Valerie M Panzarino MD

Pediatrics
Sharon Dabrow, MD
Carol M Lilly, MD
Jennifer C Takagishi, MD

Physical Medicine & Rehabilitation
Naomi A Abel, MD

Plastic Surgery
C. Wayne Cruse, MD
Michael Harrington, MD
Nicholas J Panetta, MD
David J Smith Jr, MD
Paul D Smith, MD

Psychiatry
Jean Fils, MD
Amanda G Smith, MD

Pulmonary Disease
Kapilkumar N Patel, MD
Ricardo Restrepo-Jaramillo, MD

Rheumatology
John D Carter, MD

Surgery
Michael H Albrink, MD
Christopher G DuCoin, MD
Paul C Kuo, MD

Urology
David J Hernandez, MD

Vascular Surgery
Murray L Shames, MD

Colon & Rectal Surgery
Robert D Bennett, MD

Urology
Kevin Heinsimer, MD

USF Health researchers publish on naturally occurring mutations of SARS-CoV-2 main protease gaining resistance to nirmatrelvir

In the war against deadly viruses, the enemy often wears camouflage. The challenge is how to spot an elusive foe and declare victory before more lives are lost.

One promising weapon has been the COVID-19 medication Paxlovid, which was introduced for emergency use late last year with much promise as an effective drug in keeping infected people out of the hospital.

However, researchers from USF Health, Rutgers University, and Catholic University of America are investigating how mutations of SARS-CoV-2 develop resistance to nirmatrelvir – the main component of Paxlovid. Their research has been published on the on-line preprint server bioRxiv and is currently undergoing peer-review.

The emergence of SARS-CoV-2 variants with mutations in the main protease – or M^pro – have raised the alarm for the possibility of natural M^pro mutations, which make “nirmatrelvir less effective in treating COVID-19,’’ said Dr. Yu Chen, PhD, associate professor in the Department of Molecular Medicine in the Morsani College of Medicine at USF.

From left, Dr. Yu Chen and Dr. Eric Lewandowski.

Created by Pfizer, Paxlovid is taken orally and has proven to treat severe disease from SARS-CoV-2 infections, which often require hospitalization. Nearly 90 million people in the U.S. have been infected with COVID-19, and more than 1 million have died.

If the virus can bypass Paxlovid, experts say, they could lose a major therapy in battling the pandemic.

“While vaccines have been quite effective in preventing serious symptoms of COVID-19, the therapeutic options to treat it are very limited and only two oral drugs have been approved in the U.S. so far,’’ Dr. Chen added. “Resistance makes nirmatrelvir less effective in treating COVID-19.’’

Led by USF’s Dr. Chen and Dr. Jun Wang of the Department of Medicinal Chemistry at Rutgers, the team cloned and purified many M^pro mutant proteins that occurred in nature, and analyzed their biological activity, including how they interacted with nirmatrelvir.

“We found many of them retained significant activity of the original protein, while showing resistance to nirmatrelvir,’’ Dr. Chen said, adding that their activity was less affected by the drug. “We are currently combining some of these mutations to study whether several mutations together can allow the protein to be even more resistant to the drug.’’

Viruses tend to mutate quickly enough to evolve immunity to monotherapy treatments that bind to only one protein, said members of the Rutgers team. Combination treatments, with multiple drugs that bind to multiple target proteins on the virus, tend to maintain efficacy for much longer because the virus must simultaneously mutate in several places to develop resistance, the researchers said.

The jury is still out on how effective Paxlovid will be as the virus continues to mutate and begins to disarm the drug’s weaponry. Further research could change how these battles are fought, Dr. Chen said.

“By understanding how the protein can become resistant to the drug,’’ he added, “we can better design the next generation of drugs to make them more effective and less prone to resistance development.’’

Story by Kurt Loft

Scientific research is often a low-key exercise, with fastidious people peering into microscopes and working under the radar. Seldom are they described as rising stars, but Jiajia Yang may have broken the mold.

This month, Dr. Yang became the first person to earn a PhD from USF through a new degree program within the newly opened USF Health Heart Institute.

The 30-year-old earned her degree in medical sciences from the USF Health Morsani College of Medicine, with a focus on heart disease, specifically genetic arrhythmia and cardiomyopathy gene mutations within a family.

The Heart Institute is housed within the new Morsani College of Medicine + Heart Institute building in the Water Street Tampa district of downtown Tampa. The facility, which also includes the MD degree program, opened in January 2020.

“You can’t imagine how excited I am,’’ Dr. Yang said of her degree and new career. “The most exciting part for me is that our research is really translational for patients. This isn’t just bedside to bench, but bench to bedside.’’

Originally from a small village in rural China, Dr. Yang attended medical school in Shanghai, then won a scholarship in 2015 at Descartes University in Paris. While there, she earned her Masters and learned to speak French ─ adding to her verbal portfolio of Chinese and English.

Dr. Thomas McDonald with Dr. Jiajia Yang.

After a year, she accepted a position as a research assistant at the USF Health Morsani College of Medicine and quickly showed promise as a fast and inquisitive learner, said Thomas McDonald, MD, professor in the Department of Molecular Pharmacology & Physiology. He would later work with Dr. Yang on a variety of heart-related research projects, including the role of patient-specific induced pluripotent stem cells.

“This is all technically difficult and she overcame so many obstacles,’’ Dr. McDonald said. “She really laid the ground work to help this take off.’’

During her time at USF, Dr. Yang published five research papers in peer-reviewed journals, including new findings on using patient-specific stem cells to study disease in human tissue.

“That had not been on the map at USF until now,’’ Dr. McDonald said. “Jiajia’s papers were the first.’’

Dr. Yang wasn’t shy about sharing her love for discovery.

“I don’t think I’ve ever run across anyone as enthusiastic about her work,’’ Dr. McDonald added. “She was literally jumping up and down in the hallways screaming (about the stem cells) ‘They’re beating! They’re beating!’ Her enthusiasm was contagious.’’

Armed with her degree, Dr. Yang accepted a job as resident physician in internal medicine at the University of New Mexico School of Medicine in Albuquerque. She expects to be there at least three years, but could stay longer if needed: Heart disease is the leading cause of death in New Mexico, according to the state’s Department of Health. When not working, Dr. Yang will devote time to her other passions: cooking, hiking and biking, tennis, and working out at the gym.

Dr. McDonald expects big things from his former colleague, and has no reservations about asking her to return to Tampa: “I’d like to see her career blossom and recruit her to come back to USF.’’

For more on the USF Heart Institute, visit: https://health.usf.edu/medicine/heart-institute

Written by Kurt Loft

USF Health-UT Southwestern Medical Center preclinical study suggests inhibiting PPP1R3G/PP1γ may protect against tissue damage from heart attacks, other diseases linked to inflammation

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TAMPA, Fla. (Feb. 16, 2022) – Cell death plays an important role in normal human development and health but requires tightly orchestrated balance to avert disease. Too much can trigger a massive inflammatory immune response that damages tissues and organs. Not enough can interfere with the body’s ability to fight infection or lead to cancer.

Zhigao Wang, PhD, associate professor of cardiovascular sciences at the University of South Florida Health (USF Health) Morsani College of Medicine, studies the complex molecular processes underlying necroptosis, which combines characteristics of apoptosis (regulated or programmed cell death) and necrosis (unregulated cell death).

During necroptosis dying cells rupture and release their contents. This sends out alarm signals to the immune system, triggering immune cells to fight infection or limit injury. Excessive necroptosis can be a problem in some diseases like stroke or heart attack, when cells die from inadequate blood supply, or in severe COVID-19, when an extreme response to infection causes organ damage or even death.

A new preclinical study by Dr. Wang and colleagues at the University of Texas Southwestern Medical Center identifies a protein complex critical for regulating apoptosis and necroptosis — known as protein phosphatase 1 regulatory subunit 3G/protein phosphatase 1 gamma (PPP1R3G/PP1γ, or PPP1R3G complex). The researchers’ findings suggest that an inhibitor targeting this protein complex may help reduce or prevent excessive necroptosis.

The study was reported Dec. 3, 2021, in Nature Communications.

Zhigao Wang, PhD, associate professor of cardiovascular sciences, in his laboratory at the USF Health Heart Institute. Images on the monitor depict two types of cell death: apoptosis (left) and necroptosis. — Photo by Allison Long, USF Health Communications

“Cell death is very complicated process, which requires layers upon layers of brakes to prevent too many cells from dying,” said study principal investigator Dr. Wang, a member of the USF Health Heart Institute. “If you want to protect cells from excessive death, then the protein complex we identified in this study is one of many steps you must control.”

Dr. Wang and colleagues conducted experiments using human cells and a mouse model mimicking the cytokine storm seen in some patients with severe COVID-19 infection. They applied CRISPR genome-wide screening to analyze how cell function, in particular cell death, changes when one gene is knocked out (inactivated).

Receptor-interacting protein kinase (RIPK1) plays a critical role in regulating inflammation and cell death. Many sites on this protein are modified when a phosphate is added (a process known as phosphorylation) to suppress RIPK1’s cell death-promoting enzyme activity. How the phosphate is removed from RIPK1 sites (dephosphorylation) to restore cell death is poorly understood. Dr. Wang and colleagues discovered that PPP1R3G recruits phosphatase 1 gamma (PP1γ) to directly remove the inhibitory RIPK1 phosphorylations blocking RIPK1’s enzyme activity and cell death, thereby promoting apoptosis and necroptosis.

Dr. Wang (back) and laboratory associate Ken Chen. — Photo by Allison Long, USF Health Communications

Dr. Wang uses the analogy of a car brake help explain what’s happening with the balance of cell survival and death in this study:  RIPK1 is the engine that drives the cell death machine (the car). Phosphorylation applies the brake (stops the car) to prevent cells from dying. The car (cell death machinery) can only move forward if RIPK1 dephosphorylation is turned on by the PPP1R3G protein complex, which releases the brake.

“In this case, phosphorylation inhibits the cell death function of protein RIPK1, so more cells survive,” he said. “Dephosphorylation takes away the inhibition, allowing RIPK1 to activate its cell death function.”

The researchers showed that a specific protein-protein interaction – that is, PPP1R3G binding to PP1γ — activates RIPK1 and cell death. Furthermore, using a mouse model for “cytokine storm” in humans, they discovered knockout mice deficient in Ppp1r3g were protected against tumor necrosis factor-induced systemic inflammatory response syndrome. These knockout mice had significantly less tissue damage and a much better survival rate than wildtype mice with the same TNF-induced inflammatory syndrome and all their genes intact.

Overall, the study suggests that inhibitors blocking the PPP1R3G/PP1γ pathway can help prevent or reduce deaths and severe damage from inflammation-associated diseases, including heart disease, autoimmune disorders and COVID-19, Dr. Wang said. His laboratory is working with Jianfeng Cai, PhD, a professor in the USF Department of Chemistry, to screen and identify peptide compounds that most efficiently inhibit the PPP1R3G protein complex. They hope to pinpoint promising drug candidates that may stop the massive destruction of cardiac muscle cells caused by heart attacks.

The research was supported by grants from the Welch Foundation and the National Institute of General Medical Sciences, a part of the National Institutes of Health.

Graphic created with Biorender app by Zhigao Wang, USF Health Heart Institute.