The USF Health Taneja College of Pharmacy is expanding its pharmacogenomics efforts by launching a new collaboration with Tampa General Hospital and its pharmacy team that will allow clinicians to tailor medications based on a patient’s genetic makeup. Plans include developing clinical decision support tools in the electronic health record (EHR)to support clinicians in interpreting results and guide treatment options in the presence of pharmacogenetic data.

“Our knowledge of the associations between medications and genes is evolving and published evidence exists for the many ways our own genes may predict our response to medications,” said Teresa Ho, PharmD, BCPS, assistant professor of pharmacotherapeutics and clinical research in the Taneja College of Pharmacy.

“Every patient responds differently to a medication and that may in part be explained by pharmacogenetics”

Plans for the new collaboration are underway, including identifying key stakeholders, conducting a needs assessment, and coordinating with IT teams and internal laboratories. The program’s initial efforts will require educating both TGH and USF Health providers about the project and the value of pharmacogenetic-guided treatments with a goal to eventually set up critical notifications within the EHR so that prescribing providers are alerted to any drug-gene interactions.

The pharmacogenomics expansion is also a way to expand TCOP educational opportunities, providing training and clinical rotation options for pharmacy students and residents.

Pharmacogenomics has been a focus of TCOP since its founding in 2011, and is a central component of the services offered in its Pharmacy Plus, located on the first floor in the Morsani Center for Advanced Healthcare on the USF campus in north Tampa. TCOP has since expanded the pharmacogenomics service by partnering with the USF Health Morsani College of Medicine’s Division of Genetics and Metabolism.

“Pharmacogenomics represents an opportunity to get beyond trial-and-error prescribing of medication while implementing more predictable precision to patient’s medication therapies,” said Kevin B. Sneed, PharmD, FNAP, senior associate vice president of USF Health and dean of the Taneja College of Pharmacy. “Our pharmacist graduates will become the next wave of clinicians to transform this promising portion of healthcare delivery.”

This newest expansion with TGH, while in its infancy, carries that expertise even closer to direct patient care. “We are excited to partner with the Taneja College of Pharmacy to expand pharmacogenomic services at Tampa General Hospital in the near future so that our patients, providers and pharmacists can work together toward the development of individualized care,” said Maja Gift, MHA, RPh, CPh, administrator of Pharmacy Services at Tampa General Hospital.

“Pharmacogenomics is another piece of information that clinicians can use to help optimize the patient’s treatment regimen and minimize side effects,” Dr. Ho said. “By placing the results discretely in the electronic health record, we can build an infrastructure that can preemptively alert providers to any high-risk genetic results before the prescription is sent to the pharmacy and picked up by the patient.”

The Healthcare Imaginarium for Exponential Technologies, or HIETs is the brainchild of visionary College of Pharmacy Dean Kevin Sneed

Kevin Sneed, PharmD, (standing right) dean of the USF College of Pharmacy, spoke about how exciting new technologies would be integrated into the college’s currriculum starting this fall.

TAMPA, Fla. (Feb. 22, 2018) — USF Health’s Pharmacy Dean Kevin Sneed, PharmD, announced this week several key initiatives intended to integrate advanced technologies into the student curriculum and to keep the college at the cutting-edge of innovation in education, research and patient care. He spoke Feb. 20 to a gathering of business and community leaders, as well as students, faculty and staff.

“We want our USF College of Pharmacy to remain relevant not only today, but for the next 25 years,” Dr. Sneed said.  “Right from the beginning, our mission has been to revolutionize health through innovation and empowerment… Now is the time to reimagine what education will be moving into the future.”

The initiatives are part of a newly created Healthcare Imaginarium for Exponential Technologies or HIETs.   They include the introduction in fall 2018 of virtual reality content to supplement existing curriculum and help make the learning experiences of USF pharmacy students more immersive and life-like than textbooks, online content and traditional videos.

Many of those gathered used mobile device technology to record the event.

Students will put on special eyewear to view computer-generated images they could interact with. So for instance, they might experience in 360-degree, three-dimensional context the growth of plaques in coronary arteries and what happens when a stent is inserted to clear a clogged artery.  In yet-to-be-developed ways, virtual reality technology may also seamlessly combine pharmacology with physiology to simulate the effects of treatment. For example, students could visualize in real-time the action on smooth muscle airways when a bronchodilator drug is inhaled by an asthma patient. Such advanced technology could also be harnessed by health professionals as a more engaging way to educate patients about their diagnoses and care, Dr. Sneed said.

The College of Pharmacy plans to work with MediaLab 3D Solutions, a Tampa-based digital content creator, and BioLucid, a digital health company recently acquired by Sharecare, to develop a combination of virtual, augmented and mixed reality content.

USF pharmacy student Natalie Dehaney demonstrates how virtual reality technology allows students to visualize what happens inside the body when a patient experiences atrial fibrillation. She can trigger and replay the simulation of electrical conduction in the heart. 

MediaLab CEO Bruce VanWingerden said the project will be the first time the company, which works with major corporations, has ventured into academia. “This is an exciting opportunity to work with Dr. Sneed and his staff to really look at different ways to present in a new and exciting fashion information that can be difficult to convey,” VanWingerden said. “We want to take all the innovative technology and make it easy to use to further the educational process.”

Laysa Mena, a student delegate for the College of Pharmacy, describes herself as a “visual learner” who absorbs more by seeing than reading. “So I feel implementing virtual reality with our curriculum would be very beneficial and give us a better appreciation of how drugs work in the body,” she said.

Dr. Sneed announced a key initiative known as the Botanical Medicinal Research Consortium, which will team USF researchers and clinicians with local companies to conduct evidence-based  clinical research on whether non-euphoric forms of cannabis may benefit patients with certain diseases.

Another key initiative, known as the Botanical Medicinal Research Consortium, or BMRC, will bring together researchers and clinicians in USF’s colleges of pharmacy and medicine, the university’s Center for Drug Discovery & Innovation, and businesses in Tampa Bay and beyond to conduct rigorous studies on the safety and effectiveness of medical cannabis and other plant derivatives.

Many unanswered questions remain about the potential of cannabinoids, the active chemical found in the plant and elsewhere, to treat various diseases or conditions like chronic pain. The USF College of Pharmacy wants to take the lead in conducting top-quality research on medical cannabis and find the correct noneuphoric formulations that may benefit patients and their overall health, Dr. Sneed said.

Mark Kindy, PhD (left), professor of pharmaceutical sciences, is the College of Pharmacy’s liaison for the Botanical Medicinal Research Consortium, and Kevin Olson, PharmD, MBA, assistant professor of biopharmaceutics and clinical research, is the liaison for the Entreprenerial Academy, a collaboration with the Muma College of Business. 

“Plant-derived compounds are the future of medicine, and we’re looking forward to collaborating with the University of South Florida in this area,” said Garyn Angel, chief strategy officer for ANANDA Scientific, a company that produces nonpsychoactive and nonabusive oral cannabinoid health products. “Evidence-based clinical research is needed for cannabinoids to enter Western medicine.”

Dr. Sneed also announced that the BMRC would collaborate with the UCLA Cannabis Research Initiative at the UCLA Semel Institute for Neuroscience and Human Behavior, one of the first academic programs dedicated to investigating cannabis to lead public policy and public health decisions.

Other HIETs initiatives include:

• With the College of Engineering, USF Pharmacy will work to advance personalized medicine that tailors therapy based on an individual’s genetic makeup. As the technology of medicine and drug development continues to shrink down to the nanoscale, USF has also started a Pharmaceutical Nanotechnology master’s program to teach students how to deliver medications in new, more precise ways.

• The College of Pharmacy will join forces with the Muma College of Business to create an Entrepreneurial Academy that inspires innovation and start-up companies.  The aim is to help pharmacists think like entrepreneurs so they can better enhance heath care outcomes and cost-effectiveness.

• Clinical trials: Through its WE-CARE program (Workgroup Enhancing Community Advocacy and Research Engagement), the College of Pharmacy partners with key stakeholders to increase participation of minority and medically underserved populations in clinical trials.  The program seeks to ensure that all communities have access to genomic clinical research as technology advances.

-Photos by Torie Doll, USF Health Communications and Marketing

Studies led by USF’s Dr. Stephen Liggett shed light on genetic variability of adrenergic receptors and how they might best be used to treat disease

Dr. Stephen Liggett, who leads the research enterprise for the Morasani College of Medicine and for USF Health, also oversees a genomics laboratory working on NIH-funded studies. Behind him is a radioligand binding machine used to determine the number of receptors in each cell.

While significant progress has been made managing asthma over the last two decades, about half of all asthmatics achieve optimal control of this chronic inflammatory disease using currently available medications.  Similarly, only about 50 percent of patients with congestive heart failure, which occurs when the heart is too weak to pump enough blood to meet the body’s needs, have an average life expectancy of more than five years.

More still needs to be  known at the molecular level about these common diseases to identify potential new targets for drug therapies, said Stephen B. Liggett, MD, associate vice president for research at USF Health, vice dean for research at the Morsani College of Medicine, and professor of internal medicine and molecular pharmacology and physiology.

What ties these two diseases together are the receptors on cardiac muscle and on smooth muscle of the airways. Dr. Liggett’s laboratory helps shed light on the genetic variability of adrenergic receptors and on how these receptors can best be used for treatment. The genetic studies have been particularly useful in developing the concept of pharmacogenetics, a tailoring of therapy based on an individual’s genetic makeup, for heart failure and asthma.

“Twenty years ago we had a handful of medicines for high blood pressure, and today we don’t use any of them. Now, we have a whole new group of more effective (antihypertensive) drugs with much fewer side effects,” he said.  “And, I’m sure that one day, we’ll have more tools in our toolbox to better treat heart failure and asthma – drugs that work better for subgroups of people as defined by their genetic makeup and environmental exposures.”

 Dr. Liggett comments on some of his laboratory’s contributions to the field over his career.

The research team led by Dr. Liggett, center, includes Ashley Goss, Hiwot Zewdie, Donghwa Kim, PhD, and Maria Castano. Not pictured: Alexa Woo, PhD.

Mining a “superfamily” of receptors for better drug targets

Dr. Liggett leads a USF team that studies the genetic, molecular biology, structure and function of G-coupled protein receptors, or GPCRs, the largest family of human proteins.  More than 800 GPCRs have been discovered within cell membranes in the human body, Dr. Liggett said, and one or more of these receptors plays a role in virtually everything the body does, including controlling thoughts in the brain, sight and smell, uterine contraction and relaxation, blood pressure, cardiac, lung and kidney function, to name just a few.

Consequently, malfunctions of GPCR signaling pathways are implicated in many chronic diseases including asthma and cardiovascular diseases.  Already this “superfamily” of receptors accounts for nearly half the targets of all prescribed drugs. But, a deeper understanding of the dynamics of the GPCR signaling network and how it maintains a healthy cell or responds to pathogens could lead to the design of drugs that more precisely target diseases with greater effectiveness and fewer side effects.

Dr. Liggett began his work with GPCRs in 1988 as a Howard Hughes Institute postdoctoral research fellow in the Duke University Medical Center laboratory of mentor Robert Lefkowitz, MD. Dr. Lefkowitz was awarded the 2012 Nobel Prize in Chemistry with Brian Kobilka, MD, for groundbreaking discoveries revealing the inner workings of GPCRs.

Building upon his interest and advanced training in pulmonary and critical care medicine, Dr. Liggett began early in his career to concentrate on one of the classes of GPCRs known as adrenergic receptors, which are stimulated by the hormone epinephrine and the neurotransmitter norepinephrine. They are involved in increasing the rate and force of contraction of the heart, as well as constriction and dilation of blood vessels throughout the body and of airways in the lung. For the last 28 years, he has been continuously funded by the National Institutes of Health (NIH) to study the molecular basis of beta-adrenergic receptors in asthma.

Biological scientist Ashley Goss

Dr. Liggett is the principal investigator of a four-year, $1.12-million R01 grant from the NIH’s National Heart, Blood and Lung Institute (NHBLI) that seeks to understand how beta-adrenergic signaling is regulated to influence the development and treatment of asthma. Over his career, he has also been awarded millions of dollars in NIH funding to explore the role of genetic variations of GPCRs in heart failure, including whether those variations may alter how effectively drugs work in individual patients.

Bitter taste receptors in a new place

Dr. Liggett is also currently a project principal investigator for a five-year, $2-million NHBLI P01 grant examining how airway smooth muscle bitter taste receptors might be applied as new treatments for asthma and chronic obstructive pulmonary disease.

Using a genomics-based method that Dr. Liggett pioneered, his team had previously identified bitter taste receptors, initially thought only to exist on the tongue, deep inside the lung at the airway smooth muscle and demonstrated they act to open the airway. “When activated, they appear far superior to the beta-agonists commonly prescribed to patients to open their airways during an asthma attack,” said Dr. Liggett, who published the discovery and the need for alternatives to current bronchodilators in Nature Medicine and other journals.

Overall, discoveries emerging from Dr. Liggett’s research have yielded more than 250 peer-reviewed papers, many highly cited and appearing in top journals such as Nature Medicine, Science, Proceedings of the National Academy of Sciences, and the New England Journal of Medicine. His work has been cited by other papers more than 26,000 times. He also holds 18 patents detailing potential new targets for drug therapy or genetic variations of known drug targets and how they might be used to predict response to medications and customize treatment.

 The serendipity of finding bitter taste receptors on smooth airway muscle in the lungs

Laboratory assistant Hiwot Zewdie

Among some of his laboratory’s major findings:

– While at the University of Maryland, Dr. Liggett’s team worked with colleagues at the University of Wisconsin-Madison to sequence for the first time the entire genomes (more than 100 different strains) of all known rhinoviruses, a frequent cause of respiratory infections including the common cold. The groundbreaking work, published on the cover of Science, provided a powerful framework for large-scale, genome-based epidemiological studies and the design of antiviral agents or vaccines to combat rhinoviruses. “I originally suggested sequencing 10 strains, and then my collaborator asked why not do them all,” he said. “This made the difference between a mediocre proof-of-concept paper and a full article in Science. I learned that it is important to think big if you want to make a real difference”

–  Discovered and characterized genetic variations that may predict which patients with congestive heart failure respond best to a life-saving beta-blocker drug.  These landmark studies occurred over several years and were published in Nature Medicine twice, and the Proceedings of the National Academy of Sciences three times. “This is a good example of the progression of an idea over time, where every year or so an unexpected turn of events occurred, and new insight was gained,” he said.

– While at the University of Cincinnati, Dr. Liggett, working with colleagues at Washington University and Thomas Jefferson University, found that a genetic variation of an enzyme, which inhibits beta-adrenergic receptor signaling, confers “genetic beta-blockade” in cardiac muscle and protects against early death in African Americans with heart failure.  The findings, published in Nature Medicine, provided insight into individual variations in disease outcomes. Another key study from Cincinnati revealed that a certain combination of genetic variants within a single gene conferred low vs. excellent responses to inhaled beta-agonists in treating asthma. These combinations, called haplotypes, had never been identified in GPCRs. The work was published in Proceedings of the National Academy of Sciences.

Dr. Liggett’s groundbreaking research sequencing all known human rhinoviruses, a frequent cause of respiratory infections, was featured on the April 3, 2009 cover of the journal Science.

Advancing outside his field of study

Dr. Liggett joined USF Health in 2012 from the University of Maryland School of Medicine in Baltimore, where he was associate dean for interdisciplinary research and professor of medicine and physiology. He received his MD degree at the University of Miami and completed both a residency in internal medicine and fellowship in pulmonary diseases and critical care medicine at Washington University School of Medicine and Barnes Hospital in St. Louis, MO.

Within two years, he advanced from a postdoctoral research fellowship in Dr. Lefkowitz’s laboratory at Duke to tenured associate professor and director of pulmonary and critical care medicine at the University of Cincinnati College of Medicine.  By the time he left Cincinnati for the University of Maryland in 2005, he held an endowed chair in medicine and directed the university’s Cardiopulmonary Research Center.

Though he had no significant wet-lab experience, Dr. Liggett was fascinated by the emerging science called “molecular biology” and was undeterred from branching into a field of study in which he had no formal training.

He secured a position as assistant professor at Duke following his fellowship there, and figured out how to sequence adrenergic receptor genes from a patient’s blood. While routine now, such genetic testing had not been done previously.  He unexpectedly kept finding multiple variations (called polymorphisms or mutations) in genes coding for the same receptors, so he sought out the advice of some classic geneticists.  At the time, Dr. Liggett said, their traditional thought was modeled after diseases like cystic fibrosis — if a person had the genetic mutation they developed the disease, if the mutation was absent they did not.

“There was no consideration for common genetic variants and how they might affect disease risk, progression, or response to treatment. It simply was not in their thought process,” Dr. Liggett said. He was told “it’s probably nothing and don’t quit your day job.” He did not take their advice.

 Some advice Dr. Liggett would give to emerging young scientists

Assistant professor Donghwa Kim, PhD

Instead, he returned to the laboratory to sequence and clone receptors from many different populations with asthma and heart failure, showing that the receptor genes did indeed differ from one individual to another, generally with several common “versions.” His team also created “humanized” mice expressing the human genes for asthma and heart failure so they could begin to understand the physiology of the receptors. They began to find that some genetic alterations increased receptor function, some decreased the drug’s affinity to bind (responsiveness) to a receptor, and still others altered how the receptor was regulated.  And, through NIH-supported clinical trials, the researchers correlated outcomes observed in patients undergoing drug therapies with the genetic variations uncovered in the laboratory.

“If there’s a lesson to be learned here by young investigators, I’d say it’s that you can collect information from experts in the field, but you need to use your gut to ultimately decide on whether to pursue a line of research or not,” Dr. Liggett said.

Personalized medicine challenge: Common diseases, multiple genetic variations

Realizing personalized medicine’s full potential will require a better understanding of how environmental variables – including diet, exercise, the gastrointestinal microbiome (gut bacteria) and toxin exposure – combine with genetic variations to affect disease and its treatment, he said. “Personalized medicine faces its greatest challenges in the common diseases like asthma, atherosclerotic heart disease and heart failure, because they involve multiple variations in multiple genes that interact with the environment to give you a disease – and also provide a set-up for unique ways to treat the disease.”

Biological scientist Maria Castano

Dr. Liggett was one of the first physicians recruited for what would become the USF Health Heart Institute.  He recalls that he still had the letter of offer in his pocket when he stood before the Hillsborough County Commission in 2012 to help USF Health leadership pitch the need for a cardiovascular institute to include a focus on genomics-based personalized medicine.  The county joined the state in funding the project, and Dr. Liggett was instrumental in the early planning stages of the Heart Institute before the arrival of its founding director Dr. Samuel Wickline.  The institute is now under construction in downtown Tampa as part of the new Morsani College of Medicine facility, a key anchor of Water Street Tampa. Already, 21 of the 31 institute’s biomedical scientists who will investigate the root causes of heart and vascular diseases with the aim of finding new ways to detect, treat and prevent them, have been recruited.

“There’s an excitement here and philosophy of excellence that’s rewarding to see,” Dr. Liggett said. “We have a strategic plan in place, including moving ahead to expand research in cardiovascular disease, infectious disease and the microbiome, and the neurosciences. Our departments are recruiting at a good pace, and the faculty we’re bringing in all have NIH funding and are highly collaborative.”

Dr. Liggett is an elected fellow of the American Association for the Advancement of Science – one of only five Morsani College of Medicine faculty members to receive that prestigious honor.  He is also an elected Fellow of the National Academy of Inventors and the American College of Chest Physicians. Last year, he was one of 30 scientists nationwide selected to join The Research Exemplar Project – recognition of his outstanding reputation as a leader whose high-impact, federally-funded research yields novel and reproducible results.

Over his career, he has served on several NIH study sections and on the editorial board of high-impact journals relevant to fundamental biochemistry as well as heart and lung diseases.  He is currently editor-in-chief of the Journal of Personalized Medicine.

 The potential of new treatments for asthma and heart failure

Dr. Liggett holds 18 patents detailing potential new targets for drug therapy or genetic variations of known drug targets, which might be used to predict response to medications and customize treatment.

Some things you may not know about Dr. Liggett:

• He has asthma, which helps motivate his research toward finding better treatments for this common lung disease affecting one in 12 people in the United States.
• Restores vintage cars, primarily DeLoreans. Although he recently finished bringing a funky lime green 1974 Volkswagen Thing back to life, and over the holidays restored a 1973 VW camper. 

• Lives with wife Julie on the beach in Treasure Island, where they enjoy surfing, paddle boarding, and photography.
• Has three children – Elliott, an engineer at NASA’s Jet Propulsion Laboratory at Cal Tech in Pasadena, CA; Grace, who recently completed her master’s degree in public health at USF; and Mara, an undergraduate student studying social work at Florida Atlantic University, and two step-children — Madison, an undergraduate at the University of Florida, and Tripp, a senior at St. Petersburg Catholic High School. He also has three grandchildren, ages 2 to 9.

Photos by Sandra C. Roa, and audio clips by Eric Younghans, University Communications and Marketing

Chronic stress and burnout are prevalent among more than half of health care professionals, including medical students. That is why The International Association of Medical Science Educators (IAMSE) is now featuring a series of web seminars Jan. 5, Creating a Culture of Well-being at an Academic Health Center.

“We are trying to be more aware and increasingly proactive in identifying students who potentially display signs of burnout.” said Bryan Bognar, MD, vice dean for Educational Affairs at the USF Health Morsani College of Medicine (MCOM).   “This seminar series is an opportunity for us to pause and reflect on these important topics that are of significant concern to all medical educators.”

Burnout is defined as a syndrome of emotional exhaustion, depersonalization, and low personal accomplishment leading to decreased effectiveness at work. Some key identifiers of burnout include excessive workload, an inefficient work environment and inability to maintain a health work-life balance.

A 2015 study by the American Medical Association and the Mayo Clinic concluded that burnout rates significantly rose in 2014 compared to 2011. Dr. Colin West, professor of medicine, medical education and biostatistics at the Mayo Clinic College of Medicine, called the burnout rate a “public health crisis” during a Jan. 5 web seminar. Statistics show that more than 500,000 medical professionals, across all disciplines, showed signs of burnout. Additionally, more than 40,000 cases were reported among medical students.

“Burnout is cyclical. To me, the only way to prevent burnout in medical school is to say ‘it’s okay for me to step away to do something I love that’s not related to medical school’,” said Vinodh Chandra, third-year medical student at MCOM. “This is an issue I’ve had to deal with personally. In my experience, it’s not just one single stressor at one point in time. It’s multiple demands and chronic demands that turn into perceived stressors that, over time, will wear someone out emotionally.”

One step MCOM has taken to prevent burnout is conducting the Collegia Olympics. Student groups will participate in a six-week competition designed to build healthy habits and promote healthy lifestyles. Groups have the opportunity to earn points by:

• Attending group fitness classes.
• Completing a resistance workout.
• Drinking eight cups of water per day.
• Walking 10,000 steps per day.
• Sleeping a minimum of seven hours
• Completing a physical exam or body composition exam.

Other services provided include an MCOM learning skills specialist, an aid for those experiencing academic challenges and who is readily available for students to talk to, and the USF Health Wellness Program.

“To be a good medical student and ultimately a good physician, building healthy habits and promoting healthy lifestyles are a must to prevent burnout and recover from burnout. However, identifying burnout is up to the students,” said Chandra. “Students need to be equipped with the knowledge and awareness to be able to identify burnout. The college does a tremendous job of providing resources to the students in order to address burnout.”

The IASME web seminars will continue every Thursday at noon until Feb. 2. The remaining sessions include incorporating mind-body medicine by Adi Haramati, PhD, and cultivating resilience by Michael Krasner, MD. Register for the seminars at http://bit.ly/IAMSE2017.

Story and photo by: Freddie Coleman, USF Health Office of Communications.

USF Health researchers weigh in on mouse avatars for personalized cancer therapy

Imagine a type of personalized treatment where mice serve as surrogates to treat human disease.

A newly emerging approach investigating the development of mouse “avatars” — named after the virtual characters in online games – involves implanting tumor samples from patients into immunodeficient mice where the human tumors grow.  The mice are propagated so that subsequent generations can be used to test drug combinations to find the most effective regimen for their patient counterpart.  The mouse avatars could help tailor the treatment to the individual patient, eliminating the harmful side effects and costs associated with non-targeted chemotherapies.

Vrushank Dave, PhD, with doctoral student Prerna Malaney, the lead author of the Cancer Letters paper that reviews current use and future prospects of mouse avatars.

“The opportunity for patients and doctors to create ‘Mouse Avatars’ and their utilization to guide therapy, assess drug responses to predict chemoresistance and attenuate drug toxicity in itself is a great leap in clinical medicine,”  USF Health researchers evaluating avatar therapies concluded in a recent paper in the journal Cancer Letters.

However, “the technique does not come without its limitations and pitfalls,” the authors also point out.

Vrushank Davé, PhD, assistant professor in the USF Health Department of Pathology and Cell Biology, authored the review paper with doctoral student Prerna Malaney and Santo Nicosia, MD, a USF distinguished professor.

Moving beyond the traditional mouse model

Experiments using mouse models of human disease have been done for decades, but techniques for implanting people’s tumors into mice have improved in the last few years.

Much work remains before mouse avatars become mainstream in cancer therapy, but Dr. Davé said patient-derived tumor xenografts, or PDTX, offer promise to more accurately predict how well drugs will work in a particular individual.

That’s because the tumor implanted in the mouse more accurately mimics the patient’s own genetic variations. These genetic variations among patients influence clinical trial results, and patients in the trials often do not represent the heterogeneity associated with the increasing racial and ethnic diversity in our population, Dr. Davé said.

“So, a drug may or may not work as expected for a given patient being treated.  The mouse avatar obviates this pitfall, because the genetic background of the patient and the PDTX is the same.”

Mouse avatars may be particularly useful in cases where patients are too sick to participate in clinical trials or for patients with rare cancers who have no clinical trial options, Dr. Davé said.

Mouse avatars offer the promise to more accurately predict how well drugs will work in a particular patient. Avatar is derived from the Sanskrit word “avatarah,” meaning the embodiment or manifestation of a person in a different version.

Challenges of perfecting a personalized mouse

Among the challenges of developing a personalized mouse cited by the researchers:

–         While the tumor is human, the three-dimensional environment in which the tumor grows — the connective tissue, blood vessels and other surrounding structures – is still mouse-made.

–         The cost of growing and testing the mice with combinations of potential anticancer drugs can be prohibitive –thousands of dollars — and is not yet covered by health insurance.  But that may change as the xenograft systems continue to improve, patient and clinician interest grows, and more companies commercialize PDTX for drug development and medical treatment.

–         It can take months to successfully graft the tumors and generate the test-ready mouse avatars, so many patients may not live long enough to benefit.

Meanwhile at USF, the work done in Dr. Davé’s laboratory has implications for advancing the clinical application of mouse avatars.

Using mice to advance cancer stem cell discoveries

His team creates mouse models of lung cancer to study the molecular profile of stem cells that initiate the disease.

These mice have been genetically-engineered to develop lung tumors that mimic the human disease. The researchers isolate cancer stem cells harvested from the mice and then transplant them back into the rodents to study the stem cells’ ability to multiply and spread to other parts of body.

The lung cancer stem cell research done in Dr. Dave’s laboratory has implications for advancing the clinical application of mouse avatars for drug discovery and development.

“We’ve seen that cancer stem cells regenerate tumors for multiple generations when engrafted back into the mouse, providing proof of concept that these cells behave like ‘seed’ cells to continuously grow tumors,” Dr. Davé said.

Unlike most cancer cells killed by chemotherapy, radiation therapy or other advanced treatments, cancer stem cells are often not destroyed and lead to relapse, Dr. Davé said.  “It’s like cutting the grass – you get rid of the blades, but the root remains so the grass grows back.”

The next step would be to replicate the USF laboratory’s experiments with the regenerated mouse cancer stem cells using stem cells extracted from patients’ lung tumors.

If the human cancer stem cells can similarly grow for several generations in mice, the so-called avatar mice would “provide an ideal platform for identifying and targeting a select group of molecules present only in cancer stem cells,” Dr. Davé said. “It could help accelerate the drug discovery process in treating lung cancers.”

Read the NBC News story citing the USF paper

Photos by Eric Younghans, USF Health Communications

Aimed at changing the way patients tap into the expertise of their pharmacists to better manage their health, the USF College of Pharmacy is launching the USF Health Pharmacy Plus, an on-site pharmacy of the future that goes well beyond simply filling prescriptions by offering advanced support to patients, and a futuristic, hands-on setting for pharmacy student rotations.

Using the space recently vacated in the Morsani Center for Advanced Healthcare in the heart of USF Health, Pharmacy Plus will create a national prototype for providing innovative patient engagement, education and monitoring, said Kevin B. Sneed, PharmD, professor and dean of the USF College of Pharmacy.

“The entire space offers technology at its core while providing a personalized experience with on-site pharmacists who are part of the entire healthcare team,” Dr. Sneed said. “It will be patient-centric  to optimize health.”

Among the offers will be an Rx robot that will dispense a vast majority of the medications, freeing the pharmacist to engage in therapeutic patient care. A system of integrated electronic medical records will provide seamless care with other health providers. A range of apps for tablets, smartphones and laptops will arm patients with ways to find more information and tools to help them manage their medications. QR codes will direct patients to the web for more details about their condition and the medications prescribed for them, including web videos that show how to properly use the medication and the side effects to look out for. A private space will be available for the emerging clinical applications of personalized pharmacogenomics counseling, and will explore innovative methods for pharmacists to interact with patients. Telehealth will be available to patients to enhance their communication experience with the pharmacist. And mobile health devices will be on display in the pharmacy for patients to learn how to more efficiently engage in managing their health.

The new USF Health Pharmacy Plus is scheduled to open in June.

From left, rising seniors in the USF College of Pharmacy ready to rotate through USF Health Pharmacy Plus are Dominique Nguyen, Mark LaBossiere and Kevin Cowart.

The new laboratory, focusing on genomic science to find new diagnostics and therapies for cardiovascular disease, was built with the support of Hillsborough County

Framed patents lining a wall in the newly opened USF Health Heart Institute Genomics Laboratory contain scientific language like polymorphisms and adrenergic receptors.  But application of the entrepreneurial research described in those patents may lead to new therapies based on an individual’s DNA or predict which patients are most likely to benefit from existing drugs.

“It’s ground breaking,” Stephen Klasko, MD, CEO for USF Health and dean of the Morsani College of Medicine, said of the research behind the patents held by Stephen Liggett, MD, who was recruited last year to lead the university’s genomics and personalized medicine research and who will direct the new laboratory.

L to R: Dr. Stephen Klasko, CEO of USF Health and dean of the Morsani College of Medicine, and Dr. Stephen Liggett, vice dean for research at MCOM, with Hillsborough County Commissioners Ken Hagan (chair), Sandra Murman and Mark Sharpe.

Dr. Klasko welcomed university and community leaders May 14  to the grand opening of the 7,550-square-foot laboratory, built on the fifth floor of the USF Health Byrd Alzheimer’s Institute. The celebration was an opportunity to thank Hillsborough County Commissioners for their forward-thinking support of the transformative space focusing on genomic science within the Heart Institute, and showcase how USF Health is transforming health care.

“A lot of people talk about molecular genomics and regenerative therapies, and a lot of people are doing great clinical research,” Dr. Klasko said. “We’re going to be the first place to bring together all that technology and research to really get something done on behalf of patients.”

Shelled-in space at the USF Health Byrd Alzheimer’s Institute was built out to house the Genomics Laboratory, so that basic science research could begin before construction of the freestanding USF Heart Institute. The cost of the laboratory’s construction, equipment and initial recruitment of researchers, was $2 million, half of which was funded by an economic development grant from Hillsborough County.

Last year, the state and country awarded USF a total of $8.9 million to move forward in creating a Heart Institute that will pursue innovative research to find new diagnostics and therapies for cardiovascular disease – a leading cause of hospitalizations, deaths and lost productivity in Florida and nationwide. The Legislature approved a second appropriation of funding for the Institute this session, and a final appropriation is expected next session.

Dr. Klasko welcomed university and community leaders attending the grand opening of the USF Heart Institute Genomics Laboratory.

The Institute’s proposed location will be in the center of the university’s health campus, which includes Moffitt Cancer Center, the Byrd Alzheimer’s Institute, and the Morsani College of Medicine and James A. Haley Veterans’ Hospital. The research facility will also be near Florida Hospital Pepin Heart Institute, which is collaborating with USF Health on the local arm of a national clinical trial testing a new gene treatment for heart failure.

This proximity of these leading medical institutions will help the Heart Institute create meaningful research collaborations and leverage vital resources “that will make the real difference,” said Leslie Miller, MD, director of the USF Health Heart Institute.

“It’s an exciting time,” Dr. Miller said. “New drugs and biologic therapies we’ll discover here hopefully will have an immediate impact and translate into a reduction in cardiovascular mortality.”

The 15 patents lining one wall of the Genomics Laboratory were issued to Dr. Liggett and colleagues for genomic research discoveries applicable to diagnosis and treatment.

Dr. Liggett, vice dean for research at the USF Health Morsani College of Medicine, said the genomics laboratory is the “seed” for the larger Heart Institute to come.

The laboratory is equipped with state-of-the-art machines for sequencing DNA.  That and other advanced technology will allow USF researchers to study the differences in DNA among individuals to help unravel how diseases emerge and to discover targeted therapies tailored to the patient’s genetic makeup.

The scientists who work in the lab will address such questions as: Do certain genetic variants predispose an individual to certain diseases?  Do they modify the course, or severity, of particular diseases? Can they predict an individual’s response to treatment?

“This whole concept of one drug fits all, which we know doesn’t really work, is going to stop right here,” Dr. Liggett said.

While the new genomics lab will initially focus on heart research, it will eventually branch out to other diseases. “In fact,” Liggett said, “one cannot study heart disease without also studying atherosclerosis, obesity, diabetes and metabolism, to name a few. So, we will be comprehensive.”

Dr. Miller outlines plans for the freestanding USF Heart Institute, which will be constructed in the center of the USF Health campus near other leading health institutions.

Dr. Liggett, who explained what scientists will do in the new genomics laboratory, holds up a test tube, which he said contains his DNA. “It’s labeled sample #1, because, back in 1991, I was the first person whose DNA I ever studied.”

In March 2012, Dr. Liggett and Dr. Miller joined Dr. Klasko in appearing before the Hillsborough County Commission to lay out the visionary plan for creating the USF Health Heart Institute.

“Given the importance of the University of South Florida as a key economic engine and its standing as a research leader among universities, it was an easy decision for the Board to support this lab,” said Ken Hagan, chair of the Board of County Commissioners. “When innovative thinking is matched with widespread community support, dramatic change can occur.  It will mean healthier lives for all and a healthier economic environment for Tampa Bay.”

Hal Mullis, vice chair of the USF System Board of Trustees, leads the board’s Health work group.

Hagan credited his fellow commissioner Mark Sharpe with championing the proposal for the institute.

“The transformation of health requires radical thinking and brave disruptors who aren’t afraid to challenge the status quo,” Sharpe said. “Health care and heart care is going to be changing right here in Tampa Bay, and we’re thrilled to be part of it.”

Ken Hagan, chair of the Hillsborough County Commission, said the county was proud to partner with a leading research university and the state to pursue the creation of the USF Heart Institute.

Commissioner Mark Sharpe said transforming health and heart care requires disruptive innovation, and Tampa Bay is ready to meet the challenge.

The commissioners attending the opening donned white lab coats and helped unveil a plaque recognizing the county’s contribution to advancing genomic research at the USF Heart Institute.

While economic development is a critical piece of the Heart Institute’s evolution, Dr. Liggett noted that the ultimate goal of the research is to improve and save lives.

“I’ve been at the bedside of patients with heart disease, asthma, COPD and other diseases,” said Dr. Liggett, a physician with basic science expertise.  “Patents, jobs and spin-off companies will come out of our work here, but in the end we want to help the human condition – and that is what we are going to do.”

 Photos by Eric Younghans, USF Health Communications

USF Health’s Dr. Rebecca Sutphen will lead the national, collaborative research expected to help personalize and improve cancer care

TAMPA, Fla. and HARTFORD, Conn. (May 9, 2013) – The University of South Florida (USF) and Aetna (NYSE: AET) are launching a ground-breaking study that will examine the influence genetic testing may have on clinical treatment decisions among breast cancer patients and their doctors. Understanding the connection between genetic risk factors, treatment options and results can guide policies and services that can help patients and doctors make more informed, personalized decisions that lead to better health.

The National Institutes of Health (NIH) awarded funding to USF for the five-year American BRCA Outcomes Among the Recently Diagnosed (ABOARD) study. The study will follow 5,000 Aetna members from across the country who have been newly diagnosed with breast cancer and who are undergoing genetic testing.

Certified genetic counselors can help assess specific cancer risks in families, recommend appropriate genetic tests, and interpret genetic test results. They can also recommend appropriate personalized options for cancer screening, early detection and prevention. Individuals and their doctors can use this information to optimize care. Current research suggests that only a small percentage of breast cancer patients who have an inherited cancer risk actually receive genetic counseling and testing services. Even fewer receive this information at the time of diagnosis when it might be most useful for making surgical and other treatment decisions. 

USF Health’s Dr. Rebecca Sutphen will lead the national collaborative study.

“Research shows that many women who develop breast cancer have inherited a strong predisposition to cancer. However, many of these women are not aware of their genetic susceptibility. They also do not know that they are at high risk to develop another breast cancer or ovarian cancer in the future and that other blood relatives are at increased risk for cancer,” said Rebecca Sutphen, M.D., professor of genetics at the Epidemiology Center, USF Department of Pediatrics.

“This unique academic-industry collaboration will create a new level of research into the impact of genetic information on American cancer patients and their families. Few topics have greater potential for positive public health impact. We appreciate Aetna’s leadership and collaboration to make this important research possible.”

Dr. Sutphen, an American Board of Medical Genetics-certified clinical and molecular geneticist and expert in inherited cancer risk, will lead the national study. The multidisciplinary team will include:

• Dr. Sutphen’s research team at the USF Health Morsani College of Medicine, including co-investigators Kristian Lynch, Ph.D., James Andrews, Ph.D. and Claudia Aguado Loi, Ph.D.
• An Aetna team led by Joanne Armstrong, M.D., M.P.H., national medical director for women’s health and lead for genomic medicine
• An advocacy team led by Sue Friedman of the national non-profit advocacy and awareness organization Facing Our Risk of Cancer Empowered (FORCE)
• Marc Schwartz, Ph.D., director of cancer control, Lombardi Comprehensive Cancer Center, Georgetown University

The project will use patient-reported outcomes as well as medical claims data.  Using information from a variety of clinical settings rather than only academic centers will provide a more “real-world” view of current care. USF and Aetna have developed an extensive research and security infrastructure to ensure the privacy and confidentiality of participant data.

“The research will provide critical information that can help ensure the benefits of advanced genetic testing and genomics can be used to guide safe, effective personalized health care. As more sophisticated tests are developed, we have a responsibility to help patients and doctors understand how to act on the information to improve patients’ health,” Dr. Armstrong says.

The new study builds on an existing research partnership between this multidisciplinary team and researchers from the American Cancer Society. The groups have been working together for the past two years, with support from the Aetna Foundation, to better understand the experiences of individuals who have had genetic tests to determine their inherited risk of cancer. The study also looked at differences in treatment, information and health outcomes among minority patients. Results are expected to be published later this year.

About USF Health
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. For more information, visit www.health.usf.edu

About Aetna
Aetna is one of the nation’s leading diversified health care benefits companies, serving an estimated 44 million people with information and resources to help them make better informed decisions about their health care. Aetna offers a broad range of traditional, voluntary and consumer-directed health insurance products and related services, including medical, pharmacy, dental, behavioral health, group life and disability plans, and medical management capabilities, Medicaid health care management services, workers’ compensation administrative services and health information technology services. Aetna’s customers include employer groups, individuals, college students, part-time and hourly workers, health plans, health care providers, governmental units, government-sponsored plans, labor groups and expatriates. For more information, see www.aetna.com. 

About FORCE
No one should have to face hereditary breast and ovarian cancer alone. For more than 13 years, Facing Our Risk of Cancer Empowered (FORCE) has been the voice of the hereditary breast and ovarian cancer community. FORCE provides support, education and awareness to help those facing hereditary breast and ovarian cancer know their healthcare options and make informed decisions. The organization is the de facto leader in guiding critical research and policy issues that impact the hereditary breast cancer and ovarian cancer community. For more information about FORCE and hereditary breast and ovarian cancer, please visit www.facingourrisk.org.

Cancer, cardiovascular illnesses and most other common diseases now have multiple medications that may work – yet none of them work on more than half the patients, keynote speaker Howard McLeod, PharmD, told an audience gathered for the 2013 USF Health Research Day Roy H. Behnke Distinguished Lectureship.

“So when prescribers are faced with choosing a medication to give a patient, which do they pick?” said McLeod, who directs the Institute for Pharmacogenomics and Individualized Therapy at the University of North Carolina-Chapel Hill. “They often make their decisions based on familiarity with drugs they know best.”

That’s because there is no way to predict with great certainty whether a patient will respond to a drug very well, somewhat, not at all – or perhaps even adversely. The result, for many patients, is a time-consuming, sometimes costly, trial-and-error approach to finding the right drug at the right dose.

Howard McLeod, PharmD, Distinguished Professor of Pharmacogenomics and Individualized Therapy at the University of North Carolina Eshelman School of Pharmacy, was the keynote speaker for this year’s USF Health Research Day.

McLeod is a prominent researcher in the emerging field of pharmacogenomics, which explores how variations in our individual genetic makeup influence how we react to drugs.  The institute he leads is working to integrate personalized into medical practice by providing the tools and tests for physicians to identify patients at high risk for toxic side effects as well as those likely to benefit from a particular treatment.

During his Research Day presentation, McLeod focused on the need to harness the growing body of information obtained from DNA analysis to attain comprehensive and more meaningful understanding of which genes are important in guiding drug therapy.

Easy-to-use informatics solutions must be in place before clinicians and pharmacists can broadly apply complex information about the multitude of genetic variations, and other factors interacting with genetic makeup, to select and dose medicines, McLeod said. Some progress is being made. For example, he said, there is now an iPhone app, called iWarfarin, that can help determine the optimal initial dose of  warfarin, a widely-prescribed anticoagulant drug, based on an individual’s genetic signature. “It’s not as fun as Angry Birds, but almost,” McLeod quipped.

McLeod challenged academic medicine to be more proactive about translating genetic discovery into applied knowledge that will mean safer, more cost-effective care for patients. “We get the grants, do the discovery, validate findings, publish papers… but then what? Are we creating the science that will help grandma?”

Stephen Liggett, MD, vice dean for research at the USF Health Morsani College of Medicine, said that McLeod’s relay race analogy of progressing from basic science discovery to validation to implementation of research and incorporation into medical practice was a good one.

“If at any one of those points, your institution or group of collaborators doesn’t pick up the pace and move the baton forward, then it’s possible all that work will not come to fruition,” said Dr. Liggett, who joined USF Health to lead the university’s personalized medicine and genomics research.

USF, known for its innovation, will move forward with implementation, Dr. Liggett said. Our relay race, he added, “could be helped along by hospital partners willing to be adventurous with us” in tackling the complex challenges and issues of pharmacogenomics and personalized medicine.

Photos by Eric Younghans, USF Health Communications

USF Health faculty members in medicine and public health scored major media hits this past week.

Stephen Liggett, MD, vice dean for research at the USF Health Morsani College of Medicine,  was among the academic  leaders in the emerging field of personalized medicine and genomics to comment in a New York Times piece about a new technologically-advanced machine  that interprets a person’s DNA blueprint for use in medicine, while keeping the highly personal data secure.     A multicenter team headed by Dr. Liggett recently identified alterations in DNA sequence, termed genetic variants, that predict which patients with heart failure can be saved from experiencing fatal arrhythmias.

Thomas Unnasch, PhD, professor and chair of global health at the USF College of Public Health, was prominently featured in a CNN Health story that depicts the misery suffered by Africans afflicted by onchocerciasis, commonly known as river blindness.  Dr. Unnasch is one of the world’s leading exerts on this rare parasitic disease spread by the bite of a black fly that breeds in fast-flowing rivers.   He chairs an expert advisory committee consulting with the Ugandan Ministry of Health on efforts to eliminate the blinding infection from Uganda by 2020.