I am Harvard Catalyst: Ali Tavakkoli, MBBS

Bench to bedside: A surgeon leverages basic science to understand an important clinical phenomenon.


Ali Tavakkoli, MBBS
HMS Assistant Professor of Surgery
Brigham & Women's Hospital

Research Summary:

Dr. Tavakkoli uses animal models and analysis of primary human tissue to understand mechanisms underlying resolution of type 2 diabetes after weight loss surgery.

Translational Activity:

Tell us about yourself and your research interests.

I am an assistant professor of surgery at Harvard Medical School and Brigham and Women's Hospital, and my clinical niche is minimally invasive weight loss surgery, including gastric bypass. One of the remarkable observations after this type of surgery is that it leads to rapid resolution of type 2 diabetes, usually within a few days, and before the patient has lost any weight. The patients often come in on several anti-diabetic medications, including insulin, and go home 2-3 days after surgery on no medication! It's quite amazing.

The KL2/Catalyst Medical Research Investigator Training allowed me to reduce my clinical responsibilities and to pursue my research more seriously.

From a research perspective, we are really interested in why this happens. We are studying the phenomenon primarily in rodents to understand the relevant molecular pathways, and then trying to identify parallel pathways in humans through the analysis of primary human tissue. Our long-term goal is to use our basic science results to develop a less invasive procedure or pharmaceutical intervention that could replicate the metabolic success of surgery and resolve type 2 diabetes without the risks of a major operation, or be offered to diabetic patients who presently do not qualify for weight loss surgery.

Our studies have suggested a role for intestinal taste receptors in regulating intestinal sugar absorption which is altered after bypass surgery. We believe this change contributes to the diabetes resolution after this operation. We have created a tissue bank from 40+ patients undergoing surgery (which includes blood samples as well as a variety of gastrointestinal tissue samples) and are validating these targets in man. We have started to think of less invasive alternatives that may replicate the anti-diabetic effect of the surgery and alter intestinal nutrient sensing, and have recently focused on inducing degeneration of selective nerves that innervate the intestine. Impairment of nerves is achieved by applying capsaicin (a pepper derivative) topically to the nerves through a surgical procedure that can be done in a minimally invasive fashion and with minimal risk.

How does Harvard Catalyst fit into your research and career?

Harvard Catalyst helped put my research on the map. I first learned about Harvard Catalyst soon after its inception and through the Pilot Funding Program. The grant application process was wonderful and made investigators look for collaborators across other disciplines and institutions. I applied during the first cycle back in 2008 and wasn't funded. The following year I applied for the next round of pilot funding as well as the KL2/Catalyst Medical Research Investigator Training opportunity, the Harvard Catalyst-sponsored K award. I was fortunate to be selected for both awards, but could only accept one! I chose the KL2 award, and believe this award was critical to my subsequent progress. At the time, I was in a situation where my clinical workload was increasing, and I was being pulled in different directions. The KL2 allowed me to reduce my clinical responsibilities and to pursue my research more seriously. It also gave me some credibility within my department and institution, and demonstrated my commitment to research. This has been really important.

The Intensive Training in Translational Medicine course taught me about
issues of intellectual property and
commercialization, among other things.

The mentorship that comes with the KL2 was also invaluable. One of my mentors was Dr. Stanley Ashley, whom I've known for a long time and has always been very supportive. My other mentor however was someone I had known less well, Dr. Joe Avruch. I approached him to request his support for my application, and despite his many responsibilities, he was kind enough to agree to it. He has been a wonderful resource and extremely generous with his time and insight. We met frequently, exchanged a lot of ideas, and he is now a collaborator on my R01 that was recently funded. This would not have been possible without the KL2 award.

I've also taken advantage of many Harvard Catalyst educational opportunities. The Intensive Training in Translational Medicine, in particular, was superb. Around the time that I took that course, we were starting to think about how we might develop a compound to target some of the pathways we were studying, and the Intensive Training in Translational Medicine course taught me about issues of intellectual property and commercialization, among other things. One of my collaborator's post-docs also attended the course, and this provided a nice opportunity for us to build on our collaboration.

I have used some of the other resources available through Harvard Catalyst. I process some of my human specimens through the Harvard Catalyst Central Laboratory. And I use Harvard Catalyst Profiles to help identify collaborators and potential funding opportunities.

So, overall, Harvard Catalyst has meant a lot to both my research and my career. It's provided some funds to help jumpstart my research, connected me with mentors and collaborators, and provided a lot of wonderful educational opportunities and resources. And all of this has come at just the right time in my career.

What insights can you offer other researchers?

I guess the one piece of insight I can offer is that you don't have to do it alone. At a place like Harvard, where there are so many cutting-edge scientists and amazing technologies, everything can feel really scattered, with many barriers to starting your research: where am I going to find the resources? how can I find potential colleagues or mentors? For many people, and especially for clinicians who are struggling to balance research with clinical duties, it can be hard to overcome these barriers.

I think Harvard Catalyst helped
put my research on the map.

I think it's important to realize that Harvard Catalyst can help with all of this. The resources and connections that Harvard Catalyst provides mean that you don't have to do it all yourself. You can use resources like the Harvard Catalyst Central Laboratory to help support your research efforts, or apply for pilot or KL2 funding to help get your project off the ground. Collaboration can really help too, and the Harvard Catalyst Profiles networking tool is a great way to identify a crucial collaborator. Harvard Catalyst can help you put it all together.

Resources Accessed

"I am Harvard Catalyst" is a series of spotlights on clinical/translational investigators, showcasing examples of innovation, collaboration, community engagement, or professional development that have been supported by Harvard Catalyst.