Research Q&A: Dr. Tim Bullock

BullockIn the latest blog post, we chatted with the University of Virginia’s Tim Bullock, Ph.D., a tumor immunologist in the Pathology Department and MRA-funded investigator. Read on to learn what he has to say about melanoma research and prevention efforts.

Can you explain a bit about your research?

I received an Academic Industry Award from MRA, which was a fantastic segue from the more basic/translational tumor immunology we were well-versed in to getting me more exposed to (and appreciative of) the challenges and opportunities that are presented in clinical tumor immunology. It really helped establish our lab in truly translational research.

The grant led us to begin to understand what goes wrong with T cells in patients with melanoma. We’re conducting research now to look at the transcriptional basis of what’s wrong with tumor infiltrating T cells, looking at the genes that control T cell function, and what signals from the tumor microenvironment influence the expression of these genes. We’re trying to understand if we can identify critical differences in genes in T cells that are failing to control tumors compared to those that either control tumors or infections, so that once we understand them, they could either be biomarkers for effective anti PD-1 therapies or provide opportunities to complement anti-PD1 therapy.

We take a collaborative approach with investigators at UVA, so I value working with clinicians and researchers from a variety of backgrounds. We work in teams to look at how targeted therapies and more traditional chemotherapies affect newer immunotherapies to understand the cumulative effects of these treatments. The hope is that this will help us identifying rational combinations of tumor-targeting therapies that will work well with immunotherapies.

Can you explain how your research is helping making a difference for patients?

Our most recent funding, as an Established Investigator, uses a fairly novel technology called focused ultrasound. It’s a way of delivering acoustic energy, as opposed to the more traditional radiation, into tumors, with the intent of causing damage to the tumor that the immune system can respond to. It’s in early stages yet, so we need to understand how innate and adaptive immunity, and the tumor, respond to this type of “insult.” This is focusing specifically on melanoma brain metastases as there is such an unmet need in this patient population. We’re trying to answer important questions, like:

  • Can we use it to treat brain metastases (similarly to how it’s being used to treat Essential Tremors and patients with Parkinson’s Disease)?
  • How does the brain’s immune components respond?
  • Can we integrate this technology with immunotherapy?

There are a lot of unanswered questions, but our goal is to get it to patients as soon as possible. We’re integrating our work with biomedical engineers and have funded this collaboratively because many people see the potential for focused ultrasound. If efficacy is the same as radiation, this technology could provide a new approach meet the challenge of these poorly served patients.

How has MRA funding helped your work?

Each stage of my career, MRA has been there. The Young Investigator Award helped get my lab up and running. And the continued support through Academic-Industry Partnership and Established Investigator awards have helped sustain my work.

The funding has been important, but I also value the collaborative network that MRA has fostered. The Scientific Retreat is a relaxed setting to chat about real challenges and new opportunities.

MRA has a real enthusiasm for thinking outside the envelope. MRA provides the building blocks and foundation to get important research moving forward. MRA is notorious for that and it’s certainly had an impact on my career.

What do you hope to see more of in the future of melanoma research?

The future is understanding how to integrate these amazing therapies we have now. We’re trying to understand each patient’s disease to select the appropriate combination of therapies to treat them.  We can almost come up with a “prescription” for each patient. We’re also talking about real-time monitoring of tumors to identify mechanisms of adaptive resistance. This could allow us to develop counter responses by figuring out how to react in near real time.

This is absolutely personalized, precision medicine, and I think melanoma researchers and the MRA are going to lead it.

Can you share a little about yourself? What do you outside of the lab?

One of the things I enjoy most is coaching soccer. Right now I’m coaching U14 girls soccer.

 

 

Gearing up for our Annual Scientific Retreat

The Melanoma Research Alliance’s (MRA) annual Scientific Retreat brings together hundreds of scientists, industry professionals, and patients from around the globe to foster collaboration in the field of melanoma research. This year, MRA will host its eighth retreat from February 24-26 in Washington, DC.

This year’s scientific sessions begin with a discussion on potential new therapy targets. Scientists from a variety of institutions, including Duke University and Sheba Medical Center in Israel, will discuss advances in the fields of targeted therapy and immunotherapy. In addition to discussing therapies, a prevention-focused afternoon session will address the pros and cons of mandatory skin screening and the self-screening process.

In efforts to include the expanding role of patients in the research process, this year’s Retreat will include a Melanoma Forum geared toward patients, caregivers, advocates and supporters. Moderated by FasterCuresKim McCleary, patients will be invited to an interactive discussion on their active involvement in research. The forum will provide an excellent venue for patients to engage in discussion and meet other individuals who share a common goal for the future of melanoma research.

flaherty, sigal, topalian

Participants at the 2015 MRA Scientific Retreat

The MRA team is excited to host this extraordinary group of individuals under one roof. Our Chief Science Officer, Louise M. Perkins, Ph.D., is looking forward to seeing so many close colleagues and friends from the melanoma research sphere. “There’s no event quite like this to share the latest in research and to build new collaborations.”

Tasheema Prince, Scientific Program Manager, joined MRA in 2015, and is anticipating her first retreat. “It’s essentially a glimpse into the collective fight to end melanoma and I’m very excited to witness a convening of bright scientific minds in the field,” explains Prince.

We hope the retreat allows individuals to build valuable relationships and accelerate momentum in the field of melanoma research, and ultimately help more patients overcome this disease.

To get more details on the Scientific Retreat visit our website to see a draft agenda and learn more about the event.

Researcher Q&A: Dr. John D’Orazio

In the latest blog post, we chatted with the University of Kentucky’s John D’Orazio, M.D., Ph.D., a pediatric hematologist oncologist, and a 2015 MRA grant awardee. Read on to learn what he has to say about melanoma research and prevention efforts.

How did you get interested in melanoma and your field of research?

I am a physician scientist who combines a clinical career in pediatric oncology with basic research aimed at understanding the molecular mechanisms of melanoma development. Kids don’t usually get melanoma, thankfully. But prevention is such an important part of combating this disease – particularly during childhood since pediatric UV exposure plays such an important causative role for melanoma later in life. My overarching interest, related to pediatric oncology, is understanding cancer predispositions.

Tell me about your research.

During my fellowship, I paired up with Dr. David Fisher, who is one of top melanoma biologists in the world and who happened to also be my ward attending on the pediatric oncology service at Boston Children’s Hospital. David approached me with a research project relating to understanding why fair-skinned people get melanoma so much more than dark-skinned individuals. We knew it wasn’t just about melanin since albinos – people with normal numbers of melanocytes but who don’t make melanin at all because of inherited defects in melanin synthetic enzymes – almost never get melanoma.

In the Fisher lab, I focused on the contribution of the melanocortin 1 receptor (MC1R) in pigmentation and melanocyte UV sensitivity. We chose to study MC1R since loss-of-function MC1R polymorphisms are very common among fair-skinned people and raise lifetime melanoma risk by about four-fold. Using a unique mouse model that I developed, David and I discovered that MC1R controlled whether a mouse’s skin would express dark or light melanin.

We found that pharmacologic replacement of MC1R signaling function, through the topical application of cAMP-promoting drugs to the mice, was enough to turn the skin from a blonde UV-sensitive and cancer-prone complexion to a heavily melanized UV- and cancer-resistant phenotype instead. We had demonstrated sunless tanning by pharmacologic manipulation of the MC1R signaling axis, suggesting that skin could be shielded from UV damage by melanin stimulation.

Since establishing my own lab, we’ve focused on other ways in which MC1R signaling enables melanocytes to resist UV damage and carcinogenesis. We’ve been studying how cAMP signaling increases the efficiency by which melanocytes recover and repair UV DNA damage.

How has MRA funding helped your work?

MRA funding absolutely lets us open up a new avenue of research that wouldn’t have otherwise been possible. We’re still focused on MC1R signaling but are now funded to study the natural hormonal regulation of this pathway in the skin. The MRA grant allows us to study how the pathway impacts melanoma risk on multiple fronts.

What do you hope to see more of in the future of melanoma research?

Melanoma incidence just keeps getting higher. Whatever is underlying it, we have to do something about it. Almost 2% of the population is going to be affected by melanoma in their lifetime. It’s a big problem, and although exciting advances are being made in the field of anti-melanoma therapeutics (especially targeted therapy and immunotherapy), it is still far better to avoid the disease in the first place. I would like to see more focus put into active melanoma prevention, not only through policy and indoor tanning regulation, sun protection, and public health aspects, but by using a science-based approach to enhance the skin’s ability to resist UV-mediated carcinogenesis.

What do you do when you’re not seeing patients or conducting research?

I’m a family guy. I have one daughter, a wife who is in science, and a dog. I love to cook, enjoy nature photography and have gotten pretty good at pickleball.

 

Learn more about MRA’s Research.

 

Research Q & A: Dr. Michael Atkins

In the latest blog series, we talked with Dr. Michael Atkins, Deputy Director of the Georgetown-Lombardi Cancer Center at Georgetown University, and a member of the MRA Medical Advisory Panel.

Michael Atkins

How did you get interested in melanoma and your field of research?

I had a couple of high school friends who developed melanoma, including someone who died during high school, so I was aware of the disease. In college, I developed an interest in cell biology and immunology. We knew at that time that soluble/diffusable factors could stimulate the immune system at a distance, but no one understood how it worked. I knew that I was interested in oncology because of my interest in cell biology and immunology and I wanted to be involved with patient care. As an oncologist, you’re always an important part of any patient with cancer’s medical team.

My fellowship in hematology/oncology was right around the time that Interleukin-2 (IL-2) was being investigated at the National Cancer Institute, and I got involved in a laboratory researching immunotherapy. The immunotherapy tended to work best in patients with melanoma. So, I was in the right place at the right time and things just came together.  My research interest in immunotherapy and my clinical and personal interest in melanoma intersected and led me to focus on this area.

Explain how your research is making a difference for people with melanoma.

One of the most surprising and gratifying aspects of my work has been seeing how many patients with melanoma can actually respond to immunotherapy. The identification of the immune checkpoints that dampen the immune response and subsequent successful efforts to block them and restore anti-tumor immunity with checkpoint inhibitors has revolutionized the way we treat advanced melanoma and some other cancers. I am continually impressed at how many patients have immune cells that can recognize and destroy their tumors once re-activated.

Further, our advances in melanoma immunotherapy have paved the way for similar advances in patients with all kinds of cancers, many of which we never dreamed of being responsive to the immune system.

Have there been any recent advances in treatment/your research that are particularly encouraging?

In my mind there are three important areas that the melanoma community is actively researching:

  1. Integrating immune therapy with molecularly targeted therapy. We’re looking at the impact of one treatment on the potential responsiveness of other treatments. What’s the appropriate sequence in patients with tumors bearing a BRAF mutation? Does the sequence make a difference? It’s an important practical question that physicians face every day.
  2. Recent work on checkpoint inhibitors suggests combination checkpoint inhibitors have an advantage over single agents. Studies are showing that patients are experiencing better outcomes if we target the multiple immune checkpoints simultaneously, so combination therapy has to be explored and we have to look at which combinations are most active in particular patients.
  3. Using biomarkers to make treatment recommendations. We’re trying to answer important questions, like who can respond best to combination or single agent therapy, and can you “rescue” patients given single agent after they have been given it if it doesn’t respond?

How has MRA funding helped your work?

We’re trying to better understand how other therapies, like molecularly targeted therapies, affect immune responses in the tumor microenvironment. MRA supports my research related to a clinical trial where we perform serial biopsies on patients’ tumors who are receiving BRAF inhibitor therapy. Our goal is to determine if there is an optimal time to start immune therapy after BRAF inhibitor therapy, and if giving it even makes sense.

Five years ago, median survival for patients with advanced melanoma was still 6-9 months and had remained constant for decades. When MRA stepped on the scene, there were new potential targets – like BRAF, CTLA4 and PD1– that had recently been identified. Funding from the MRA has been critical to expediting our understanding of how to optimally exploit these various targets. As a consequence, there is essentially no median survival for patients with advanced melanoma. We may have been able to get to this position eventually without the MRA, but the MRA support has enabled us to do so at practically light speed.

Researcher Q&A: Dr. Niroshana Anandasabapathy

In our latest research feature, we spoke with Niroshana Anandasabapathy of Brigham and Women’s Hospital, who is the recipient of an MRA Young Investigator Award. Funded in collaboration with Brigham and Women’s Hospital, Dr. Anandasabapathy’s research is titled “Expanding immune-surveillance and immunotherapy of melanoma.” Here she explains more about her research.

Anandasabapathy, NHow did you get interested in melanoma and your field of research?

I have always been really interested in why the immune system fails to detect cancer, and I completed my PhD in cancer biology while an MD-PhD student. I am a dermatologist, so melanoma is a critical concern, and as one of our more immunogenic cancers, melanoma is a fascinating and challenging area to work in.

Explain your research and how it can make a difference to melanoma patients.

Our research is geared at developing new drugs for melanoma immunotherapy. To do this, we study how the immune system responds to cancer and how we can improve that response in new ways.

What is one thing about your research that surprised you when you first started?

I am still amazed by how effective immunotherapy is. Although conceptually we thought it would work, seeing it in place is so gratifying. In my own work I am actually amazed by how little we understand about how protective vaccines work (for example, the vaccine to smallpox). A better knowledge of known vaccines could help develop therapies to improve immunity to cancer.

How has MRA funding helped your work?

We made some very intriguing findings for how the immune system maintains tolerance to itself in the skin. We feel it is likely skin cancer in general, and melanoma in particular, that can hijack these mechanisms, and this opportunity allows us to test whether that is true. With these data in hand we can develop new drugs to combat melanoma that block these pathways.

Have there been any recent advances in your research that are particularly encouraging?

We identified a particular target for drug development I believe is extremely promising. Because a drug to this target would work very differently from current immunotherapy, it could be combined with current therapies to improve responses in the 60-70% of patients for whom current immunotherapy does not work.

What do you do when you’re not seeing patients or conducting research?

I love to cook, paint, play the piano and am often with my family. We love being outside (with sun protection on of course) and traveling when possible. But I admit I also love work. I wake up every day excited by these questions and grateful to be trying to make a difference.

Learn more about Dr. Anandasabapathy’s work and our other funded Young Investigators.

Researcher Q&A: Dr. Neil Ganem

In an effort to share more about the work being done in the field of melanoma research, we are beginning a new feature on our blog to showcase some of our funded investigators. Today we’re talking with Neil Ganem, Ph.D., Assistant Professor of Pharmacology and Medicine at Boston University School of Medicine and recipient of the Jackie King-MRA Young Investigator Award.

Neil Ganem. Photo courtesy of Boston University School of Medicine.

Neil Ganem. Photo courtesy of Boston University School of Medicine.

How did you get interested in melanoma and your field of research?

My lab studies the causes and consequences of a phenomenon known as chromosome instability, which is a hallmark of solid tumors, including melanoma. Normal human cells maintain all of their genetic information on 23 pairs of chromosomes. By contrast, a common feature of human cancer cells is that they possess an abnormal number of chromosomes, a state known as aneuploidy. Though already abnormal, many aneuploid cancer cells continue to shuffle their chromosome content, often gaining and losing chromosomes with each cell division. This trait of cancer cells is termed chromosome instability (CIN).

CIN is known to facilitate tumor initiation, progression, the development of chemo-resistance, and relapse. Consequently, patients with CIN tumors have a poor clinical prognosis. One major focus of my research program is to uncover the cellular defects that generate chromosome instability in human cancer cells. Several years ago a colleagues of mine, Craig Ceol, generated a transgenic zebrafish model to expresses oncogenic BRAF specifically in melanocytes. Interestingly, Craig and I found that oncogenic BRAF, which is one of the most common causes of melanoma, acted as a potent driver of chromosome instability. My lab is now attempting to define the mechanisms through which oncogenic BRAF promotes abnormal chromosome segregation and CIN. To do this, we are using highly sophisticated microscopic techniques to visualize individual chromosomes as they separate during cell division.

How can your research make a difference to melanoma patients? 

A major focus of my group is to identify whether chromosome instability generated by oncogenic BRAF represents a point-of-weakness that can be therapeutically exploited. My lab has recently developed an innovative screening approach to comprehensively identify the proteins and molecular pathways required for chromosomally unstable cancer cells to survive and proliferate.

Ultimately, our long-term scientific goal is to develop new strategies to specifically inhibit the growth of abnormal, chromosomally unstable melanoma cells while sparing the normal cells from which they originated. We hope that by targeting chromosome stability, rather than a specific oncogene, we may ultimately develop new and innovative treatments for melanoma patients.

How has MRA funding helped your work?

The Jackie King Young Investigator Award from the MRA is supporting the salary of Sanghee Lim, an M.D./Ph.D. student in my laboratory. Sanghee is a fantastic student who has already finished his first two years of medical school. He will now spend the next four years earning his Ph.D. in my lab before completing his final two years of medical training. Sanghee is interested in pursuing a career in oncology/dermatology. This is one of the long-reaching effects of the support from the MRA: Awards provide the financial support to engage young M.D./Ph.D. candidates in projects directly relevant to melanoma, which may ultimately influence those students to make melanoma research their career ambition.

What do you do when you’re not seeing patients or conducting research?

As the father of three young boys, I spend most of my free time doing dad stuff! I spend a lot of time at playgrounds, playing sports and games, and building Legos. When I have time to myself, I really enjoy yard work and doing projects around the house. I used to enjoy playing hockey, but it’s been so long since I last played that I guess I should consider myself retired at this point.

Learn more about Dr. Ganem and all the MRA Young Investigators.

Melanoma News Round-Up, May 17

So much exciting news as we pass the halfway point of Melanoma Awareness Month!

ICYMI we shared our new video highlighting MRA’s collaborative approach to melanoma research and raising awareness.

 

We also shared Jamie’s story as she expressed ‘the reality of “surviving” stage IV melanoma.’

Next Tuesday, May 20, two exciting events will take place:

Finally, here are a few highlights of the melanoma news coverage this week:

10 Things to Know About Melanoma via ABCNews

A bittersweet story about a young mother of two who lost her husband to melanoma when he was only 28 via Delaware State News

A melanoma survivor tells teens to “rock the skin you’re in,” use sunscreen & avoid indoor tanning via WOWT

Blood biomarkers may enhance melanoma detection potentially reducing the need for invasive skin biopsies via MedicalXpress

‘Michelle’s Melanoma Army’ educates teens on skin cancer via The Anniston Star

Encouraging results for nivolumab in hopes of raising survival expectations for advanced melanoma patients via BMS News