Who’s new at OHSU? Hagai Tavori, Ph.D.

Hagai Tavori and family

Hagai Tavori, Ph.D., an assistant professor at OHSU’s Knight Cardiovascular Institute, joined the OHSU faculty in January 2014. Tavori’s research focuses primarily on lipoprotein metabolism and atherosclerosis.

Where are you from originally?
I completed my undergraduate and graduate studies in Israel where I was born and raised.  I earned my Ph.D. in clinical biochemistry at the faculty of medicine of Technion (Israel Institute of Technology), which is located in the beautiful coastal city of Haifa in Northern Israel.

What brought you to OHSU?
I came to the U.S. about four years ago for a postdoctoral fellowship at Vanderbilt University in Nashville, Tenn. I worked with Dr. [Sergio] Fazio in his atherosclerosis research unit. After two-and-a-half years at Vanderbilt, I began looking for new career and research growth opportunities. When Dr. Fazio relocated to OHSU as the director of the Center for Preventive Cardiology, I took the opportunity to join his enterprise. In addition, my wife liked the idea of moving to Portland, so that helped in making our decision.

What specific areas of research are you exploring?
In the Center for Preventive Cardiology, I’m involved in clinical, translational, and basic research related to lipoprotein metabolism. My main goal is to better understand the pathophysiology of dyslipidemia – abnormal amount of lipids in the blood – and to explore new therapeutic avenues to reduce cardiovascular risk.

One very interesting clinical research area we are pursuing involves working with patients undergoing lipoprotein apheresis. This is a procedure much like dialysis performed in patients with kidney failure, but rather than removing toxins from the blood, the process removes “bad” cholesterol. It’s a treatment that’s used as a last resort for those patients who don’t respond to other types of treatment and who are extremely high risk for cardiovascular disease. Our study is designed to estimate the ratios between plasma lipids and PCSK9, a protein that regulates plasma cholesterol levels, as an index to determine the optimal treatment interval for each individual patient. The current strategy of twice-a-month treatment for all patients derives from early studies, but personal experience shows us that some patients have a different return to baseline of their cholesterol levels. Our goal is to demonstrate that patients can benefit from a personalized frequency of apheresis, providing better outcomes and cost savings.

I’m also working with Michael Shapiro and Bart Duell on a translational study involving patients who have high Lipoprotein(a). This type of cholesterol carrier has deleterious effects, however; doctors don’t regularly test for it when ordering a lipid panel. High levels of Lp(a) are associated with heredity, and, until recently, there were no therapies to reduce levels other than apheresis. New PCSK9 inhibitor drugs recently approved by the FDA reduce Lp(a) levels, but the mechanism leading to this effect is unknown. So, we’re examining the interaction between PCSK9 and Lp(a) in patients with elevated Lp(a) levels to better understand the relationship between the two.

On the basic research side, I’m interested in understanding the role of HDL, or “good cholesterol,” in health and disease. Though the correlation between HDL levels and cardiovascular health in the general population has been known for decades, fairly recent studies have shown that raising HDL cholesterol does not provide a clinical benefit in terms of cardiovascular disease risk. The reasons for this are unknown, and there are various avenues of study being conducted to find answers. Investigators are looking at the possibility that the protein composition or particle size of HDL, rather than levels, is what’s significant. Others are examining HDL’s function of cholesterol extraction. A theory we’re exploring is that under pathological conditions, HDL is not getting into areas it needs to in order to be protective; it isn’t able to penetrate to the artery wall where plaque is starting to accumulate. Normally, HDL is produced by the liver and the small intestine and secreted to the circulation; however, in order to act in other organs, it needs to penetrate the target tissue. Our approach is to force cells in the artery wall to produce the HDL protein known as apoAI, thereby increasing the efficiency of cholesterol extraction from plaques.

What future directions of study do you want to undertake?
I’m expanding my “good cholesterol” studies into a gene therapy approach that may be applicable to humans by inserting the gene expressing the HDL protein into a plaque and then studying whether this intervention induces plaque regression. I collaborate with Jonathan Lindner and his team to test their micro-bubble approach to delivering genes to specific areas of the body.

Are you looking for collaborators in your research?
We are always open for collaborations, especially in areas of research where proteins involved in lipoprotein metabolism appear in different types of pathological conditions. We want to know more about the connection between the presence of these proteins and underlying metabolic processes. Are there links? Or does the presence of these proteins rule certain things out?

What do you like to do for fun?
Spend time with my family. I have a five year old and a two and a half year old, so we are members of just about every museum in town. We also like the outdoors, and living in Portland makes life easy. I am an amateur bike rider and will try some local racing this year.