WE’RE THRILLED TO WELCOME MELISSA B. DAVIS, PH.D., TO THE ENGLANDER INSTITUTE FOR PRECISION MEDICINE TEAM. DR. DAVIS IS A MOLECULAR GENETICIST, AND HER RESEARCH INTERESTS INCLUDE GENOMICS AND SYSTEMS BIOLOGY.
Dr. Davis is Assistant Professor of Cell and Developmental Biology, Department of Surgery, and Scientific Director of the International Center for the Study of Breast Cancer Subtypes, Weill Cornell Medical College. She is co-author of more than 20 peer-reviewed scientific journal articles.
Welcome to EIPM! You recently traveled to Ghana with fellow EIPM Member Dr. Lisa Newman, the chief of the Section of Breast Surgery at NewYork-Presbyterian/Weill Cornell Medical Center. When did you first meet Dr. Newman and how long have you two been working together?
I first met her in 2016 when I was being recruited to join her team in Detroit, but I’ve known of her research for at least a decade before then. Dr. Newman has been prolific in the clinical arena for studying breast cancer disparities in African American women and their more aggressive subtypes.
What’s it like to work with her?
She’s genuinely good-hearted, and though what she’s done is profound, she is soft-spoken about her accomplishments. She is only outspoken in her advocacy to address the disparate clinical outcomes in diverse populations. She’s been going to Ghana for over 20 years, largely funded out of her own pocket, and she’ll recruit people to come along and help with her service. There’s rarely any fanfare, she doesn’t typically do any press releases about her work, but she’s saved so many lives. She’s a great mentor and very supportive of her team, in every way.
The purpose of the trip was a combination of teaching, surgery and research. Can you tell me about each of those?
The teaching aspect on this trip was mostly lectures for Grand Rounds on genomics, cancer genetics and clinical oncology. I presented on our recent genomics studies, Dr. Newman presented on the state of surgical oncology as it applies to the setting: she described standard care in the US and how it could be modified to be applied in a place like Ghana, how to leverage what you have. And the plastic surgeon traveling with us presented on alternatives to breast reconstruction and how they can use certain resources and different techniques to overcome limitations.
Dr. Newman and her team of surgeons represented the clinical component of the trip: there was a ward full of women with breast cancer waiting for her, she reviewed all of the cases that first night we arrived, within an hour of arriving in Kumasi, and then from first thing in the morning until late at night they just did surgery after surgery each day.
The research component involved us setting up the protocols for blood collections and collecting fresh tissue to bring back to WCM for our studies.
What were some of the physical challenges you had to overcome?
When you actually get on the ground in a place like Ghana and see the limitations of your circumstances, you have to quickly adapt and make things work yourself. For example, in New York we have really nice centrifuges with digital display readings of the speed settings, timers and temperature levels. The one we had in Ghana has no displays, it just spun! There was an analog timer, but that was it. So, based on my experience of how a rotor sounds at various speeds — a skill I didn’t know I had until I needed it then — we figured out a way to adjust the speed and keep it steady. We made it work. In addition, the lack of a proper incubator was going to be a challenge, then we discovered that ‘room temperature’ was actually the temperature we needed in an incubator. The room was the incubator.
What did you learn during this trip?
The site leader gave a presentation where he said he’s seeing something new, a change in the trends of diagnoses called ‘stage migration,’ which was very interesting and encouraging. Officials visiting from other countries provided a summary of their cancer burdens, and usually it’s a similar story in each African nation, 80% mortality, and 90% of patients presenting with stage 3 or stage 4. But thanks to screening efforts, and biopsy training set up by the ICSBCS, the chief surgeons and medical directors in Ghana are seeing this stage migration where more patients are now presenting with Stage 2 instead of Stage 4. That’s encouraging.
You’re working with WCM’s Benjamin Hopkins, Ph.D. & Laura Martin, Ph.D., to grow organoids from the samples you brought back. How are they doing?
They’re growing! It was a success! Dr. Newman did about eight surgeries on this trip, which is less than usual, she spent a lot of time consulting on previous surgeries and treatment follow-up. So, from the surgeries she did this time, we brought back fresh tissue samples from four cases and have been growing three new organoid cultures. They’re stabilizing and look promising to establish a patient-derived West African organoid panel here at EIPM.
The global burden of breast cancer is rising, with disproportionate increases in Africa where fatality rates are notably higher. What role can research play in improving outcomes in places like Ghana?
While a lack of awareness about treatment options contribute to these poor outcomes, we could potentially provide targeted therapy drugs, but these therapies won’t work on the types of tumors they have.
We’re trying to establish why these aggressive forms of triple-negative tumors are prevalent, particularly in these regions. As we investigate the tumors in these African women, those tumor phenotypes will uncover mechanisms that can help us identify genetic drivers that may become targeted therapies. So as we continue to investigate this particular population and identify what’s unique about their tumor biology, it will also uncover targets for treatment. That’s how research can positively address the cancer burden in this community in the long-term – providing the foundation for better treatment options for their population (and descendant populations).
Is there a cultural stigma in Ghana around a disease of the breast?
Absolutely. In African countries, female status is embedded in womanhood and motherhood and breasts are integral to those roles. And a disease of the breast can be seen as a curse. A lot of clans or tribes don’t even have a word for ‘cancer’ in their language, so they don’t know what it really is, they just see it as something a woman has brought upon herself, so she’s ostracized and perhaps even cast-out from her community. Many women might hide their condition instead of seeking treatment.
You and your colleagues recently published a paper, “African Clinicians Prioritization of Needs in International Breast Cancer Patients,” that found regional physicians and nurses ranked education and training programs conducted in Africa as their highest priority need. Did this surprise you?
Yes and no. Anyone would say we need more resources and we need more money for this work. But without staff trained to use the equipment, then what good is it?
For example, we all saw this very expensive piece of donated equipment for radiation treatment and it’s just sitting in an unopened box because nobody knows how to put it together and properly use it – there is no support for its maintenance, etc. This machine is worth millions of dollars, but it’s still sitting unused today. The company doesn’t have a presence in Africa and nobody is ever going to come and make it work and maintain it. That’s heartbreaking.
What are the next steps for this research?
We’re building on our Pan-African genetic risk studies and a tumor immunology study. We will be publishing about the genetic diversity within Ghana. I think that one of the caveats in GWAS for breast cancer to date, when looking for the genetic pre-dispositions we see in African Americans, is lack of deconvolution in their specific sub-African ancestry.
There are tools to help African Americans learn about their ancestry, but we are even seeing genetic diversity within specific African countries. And this is just now being studied within the past ten years.
And as a result, due to encouragement for migration and inter-tribal marriages, we’re seeing genetic mixture within African populations that hasn’t been studied in the context of breast cancer before. And this may affect genetic predispositions going forward, as we uncover higher incidences of breast cancer after this genetic intermingling, suggesting another clue that there is a genetic allele in a population being inherited and transmitted through the population. Dr. Newman calls this investigation ‘Anthropologic Oncology.’ The long-term plan is to look at genetic diversity across Africa and within specific regions and countries.
What can Weill Cornell Medicine do to advance patient care in underserved places like Ghana?
WCM can continue to support clinicians like Dr. Newman who want to travel to places like Ghana, and in return to host medical professionals to come here for training.
I would love to start a summer program, to host some of those Ghanaian students to come in and learn how to do some of these procedures on the proper equipment. They would better understand the challenge we have when we visit them.
Is this the work you always wanted to do, and why?
Yes! My mother was a high school science teacher. I’d come home after school and open the refrigerator to find one of her experiments and I’d hear her yell from the other room, ‘don’t eat that!’ And whenever my school had a off day, I’d go into the office with her and be her partner in the lab, or play in the storage room where all the cool science equipment was kept. She ultimately taught life science, earth science, physical science, anatomy – all of the sciences in every grade. She gave me a very broad exposure to the sciences from very early on.
When I was in graduate school, the field of genetics was just taking off with implications for epidemiology, genetic epidemiology, and debates about eugenics were starting to clash with politics. Being from the deep south and it’s highly charged political climate, I found myself reading these stories about a genetic predisposition for African Americans to have criminal behavior, and that puzzled me. What were their data sources for these arguments, and what are these genes they claim to cause us to have criminal behavior? I wanted to understand and impact this ‘research.’
What has your transition to WCM been like?
It’s been an amazing experience so far. I’m surrounded by excellence. I expected the people and facilities to be among the best in the world. But what I didn’t expect was for everyone to be so collaborative. Here everyone seems to have a partner, and isn’t competing with each other for success. Nobody exists here as an island, and everyone is integrated into some program or some institute or some group, and I love that.
What would you do if you weren’t drawn to science?
I had a fork in the road in graduate school where I could have become a professional singer or become a scientist. And my family, mainly my mom, talked me into pursuing science. She said I could still sing on the side! And I played percussion, tenor drum was my favorite – I was in a marching show band in undergrad. My favorite drummer is Questlove from The Roots.
Any last words?
I finally love my job, like, all of my job! Usually I love parts of my job, but now I love all of my job!