Howard McLeod, PharmD

Fred Eshelman Distinguished Professor

Division of Pharmacotherapy
and Experimental Therapeutics

 

Research Interests

Howard McLeod is an internationally recognized expert in the pharmacogenomic analysis of cancer treatments.

When a drug goes through clinical trials, its effectiveness and side effects are determined based on a large population. However, that information only tells individual patients what is possible. It does not tell them what their own experience is likely to be. There are dramatic differences among people in their reaction to a particular medicine.

“In cancer and almost every other area of medicine, there are multiple drugs that work,” says Howard McLeod, who joined UNC-Chapel Hill in 2006 as the Fred Eshelman Distinguished Professor of Pharmacy and professor of medicine. “But none of them work on more than half the patients. So when prescribers are faced with choosing what medicine to give a person, they often go with the drug they know best. And because there is often no way to know with great certainty how the drug may work in that individual, it may not be the one that will benefit the patient the most.”

McLeod, PharmD, wants to help physicians get it right the first time when they select a medicine to treat cancer and other illnesses. He is heading a new research institute at the School of Pharmacy that will find ways to match medicines to the unique makeup of the people needing them.

McLeod, an internationally recognized expert in the pharmacogenomic analysis of cancer treatments,  is the director of the new UNC Institute for Pharmacogenomics and Individualized Therapy. The institute will work to create effective therapy and precise treatment options for individual patients suffering from a wide range of conditions. Initial efforts will focus on cancer therapy with planned expansion into cardiovascular disease, psychiatric disorders, and global health.

Leading the Way

Pharmacogenomics is a new field exploring how information in our genes influences our response to drugs. It involves integrating pharmacology with modern advances in genome analysis. The institute’s goal is to fully integrate personalized medicine into medical practice by providing tools and tests for physicians to identify patients at risk for adverse reactions or those who are likely to benefit from a particular treatment. IPIT researchers will also identify drug targets, such as genetic markers in tumor cells, to guide development of new drugs.

McLeod is a prominent figure in this new field. He is the author or co-author of more than 260 peer-reviewed papers, serves on the editorial board of seven scientific journals, and has given three hundred presentations in fourteen countries. He is a member of the Food and Drug Administration Subcommittee on Clinical Pharmacology and is vice chair of the NIH Cancer and Leukemia Group B Pharmacology and Experimental Therapeutics Committee.

McLeod came to UNC from Washington University in St. Louis, Missouri, where he was a professor in the Departments of Medicine, Pharmacology and Molecular Biology, and Genetics. He also served as the director of the Siteman Cancer Center Pharmacology Core there.

His research has helped identify specific genetic variations that predispose patients to risk of severe side effects or inadequate benefit from drugs for diseases including colorectal cancer and childhood leukemia. His research has also had an impact on the FDA guidelines for warfarin, a blood thinner prescribed to more than 2 million people in the U.S.

“Warfarin is a textbook example of a drug with a narrow therapeutic index,” McLeod says. “Give a little bit too much and people bleed. Give too little and they clot. You have to get is just right.”

Based on research by McLeod and others, the FDA issued new dosing guidelines because of two genes that affect how warfarin acts in patients.

“Progress is occurring; genetic information is improving the use of medicines in our lifetime,” McLeod says.

A Multidisciplinary Effort

Although based in the School, McLeod says the institute will bring together researchers from the Schools of Medicine, Nursing, Business, Law, and even Journalism to help individualized medicine become a reality. It will eventually be headquartered in the University’s Genetic Medicine Building, which is being built off of Mason Farm Road.

“It’s a level of complexity that no one person or even one school could take on,” McLeod says of the institute. “Many pharmacy graduates out there are impacting their physician colleagues, their nursing colleagues, their radiology colleagues, and others on a regular basis,” McLeod says. “They’re helping them make better decisions because of their skills, so it’s no surprise that the School is doing the same thing.”

In addition to working with other schools and departments on campus, the institute will work with many Triangle-based companies, including LabCorp and GlaxoSmithKline. Officials with the Food and Drug Administration will hold adjunct appointments with the institute.

The institute is even assisting legislators at the state and federal level who are trying to better understand how they can write bills that will help drive the agenda for individualized health care.

McLeod says that over the next three years, nine faculty members will be recruited to the institute. Five will have primary appointments in the School of Pharmacy with secondary appointments in other schools, and the other four will have primary appointments in medicine, public health, or one of the other healthcare schools with a secondary appointment in the School of Pharmacy.

At this point, the institute is still in its infancy. McLeod and others are forming the administrative infrastructure to provide a solid foundation for the institute’s major initiatives. McLeod is also seeking funding for the institute’s individual projects, which are just getting off the ground.

“There are a lot of moderate-risk, high-yield projects that could change the practice of pharmacy very quickly for the better,” McLeod says.

McLeod says that organizations such as the National Institutes of Health focus grant making primarily on science that has a safe element—research that is nearly completed and just needs final touches. One challenge the institute faces is securing initial funding for its projects, many of which are in the early stages of development.

Another challenge, and a major part of the institute’s mission, will be supporting the long-term application of the institute’s work.  McLeod hopes that the institute can award seed grants to young investigators who are entering the field of pharmacogenomics and want to conduct high-impact research. Supporting these new researchers will pave the way for future discoveries.

A Community Approach

In addition to collaborating with researchers from other disciplines and companies, the institute will also involve the people who are on the front lines delivering medications to patients—community pharmacists.

“A lot of our educational programming and the way we’re thinking about our research includes the community because, frankly, that’s where the action is,” McLeod says. “That’s where most patients are treated for disease. And if we don’t have tools that can be used by a community practitioner, we have nothing.”

McLeod has already been involved with local, state, national, and international presentations focused on helping community-based practitioners better understand pharmacogenomics.

McLeod also hopes to partner directly with community pharmacists interested in collaborating with the institute.

“I would strongly encourage any interested community pharmacist who wants to try to develop an innovative practice to contact us. If we’re not ready now, we’ll be ready soon,” McLeod says. “And the sooner we start the conversations, the better; because while we’re trying to create the future, we’re not trying to create it alone. We would love for people who are invested in having innovative practice to work with us, and we would love to partner with them to try to help create something special.”