Alexey Danilov, M.D., Ph.D., is an assistant professor of medicine (hematology and oncology), OHSU School of Medicine, and member of the Knight Cancer Institute. He focuses on treating and diagnosing patients with chronic lymphocytic leukemia (CLL) and various lymphomas. He has been at OHSU for a year, arriving in October 2014.
Where are you from originally?
I’m originally from Russia, but I did most of my training in the New England area of the U.S. I arrived in 2001 and completed my residency in medicine at Brown University and then followed that on with a fellowship at Tufts Medical Center in Boston. I then moved to Dartmouth as my wife was finishing her studies there, so I ended up as a senior fellow in Murray Korc’s lab working on pancreatic cancer. A year after I arrived, Dr. Korc left. Luckily, I received some support to work independently. This presented an opportunity to do what I wanted to do. I continued with my clinical and research interest in B-cell malignancies, and, with support of my clinical colleagues, I set up my own independent translational program in chronic lymphocytic leukemia (CLL).
What brought you to OHSU?
I moved here for a variety of reasons. Some were personal – my wife is a pathologist and was able to find a position at the VA. But more importantly, I found a many like-minded people here, people who want to bring novel therapies into the clinic. As a physician-scientist, I am eager to bring novel therapies into clinical world. So, I constantly operate at the interface between the lab bench and the clinic, meaning that I work with drugs in the pre-clinical setting and usher them into early-stage clinical development. OHSU is one of the institutions that is good at this kind of work. This is a very complicated setting, requiring depth of both basic and translational science, and OHSU has it figured out. Therefore, this was just the right place for me.
What got you interested in this particular line of research?
I was drawn to hematology oncology because of the high translational relevance of the work. It’s important to me that I work with primary human samples, so that my work is immediately relevant to the clinic. In CLL and some lymphomas, there is access to biologic material which can be used in translational studies. This is very different than studying solid tumors where access to diseased tissue may be very limited. Not only do lymphomas interest me clinically, the ability to work with lymphoma samples provides immediate relevance to my work in the lab. Another unique feature of working with blood cancers is the ability to make diagnosis on the slides. While I’m not a pathologist, I have the benefit of seeing the actual patient and that very tangible visual connection with the patient’s disease.
My specific focus in studying lymphoma is to target the leukemia cell interaction within the cell’s micro-environment. At the time I entered the field, there were a couple of new agents that targeted certain pathways, mostly the B-cell receptor signaling pathway. However, our team discovered that in addition to this pathway, there are a multitude of extraneous signals which support the life of a malignant B-cell in its niche – its niche being the lymph node of the bone marrow, not necessarily in the blood. So we have modeled the lymph node micro-environment in vitro and screened for different survival strategies of the neoplastic B-cell to identify what can be targeted in these micro-environmental conditions. Of particular interest to my team was targeting the NF-kB transcription factor, which is one of the key transcription factors induced by multiple soluble factors in the micro-environment. NF-kB works independent of B-cell signaling, the pathway of which is the primary target of current approved drugs.
What specific area of research are you working on now?
We’ve identified the new strategies outside the B-cell signaling pathways – which I describe above – and our data suggest that not only can the new strategies work by themselves, but they can work as strong sensitizers to the drugs that are already available. So we’re looking into the details of how the NF-kB pathway can be targeted. There are multiple complexities in terms of how the NF-kB pathway is induced. In addition, there are several branches within the pathway, so we’re trying to figure out which are important and which aren’t. We have a number of clinical trials underway for patients with CLL and lymphoma, some of which I based on the pre-clinical work performed by my team. The trials provide good options for folks who have just been diagnosed or those who have progressed through different treatments that haven’t been completely successful.
What do you do when you’re not at work?
Let me start by saying that I’ve lived in many places: Central Russia, throughout New England, and I’ve never been as happy as I am living in Portland. There is just so much to do – too many distractions actually. It’s almost too much for one place! We love the hiking, skiing, food, theater, biking, great music scene. This is also a great area for kids – from OMSI and Playdate PDX to kid-friendly hikes – almost too much of a good thing.