Congratulations to the UF Health Cancer Center Director, Jonathan Licht, M.D., for receiving the 2021 ASH Mentor Award. The ASH Honorific Awards are the Society’s most prestigious awards, recognizing individuals within the global hematology community who have made significant contributions to the field. These distinguished leaders will be honored during the 63rd ASH Annual Meeting and Exposition.
How does it feel to receive the Mentor Award?
It’s a great honor to be recognized by the Society because this award is not really about me; it’s about those I’ve worked with over the past 30 years in my career in academic hematology-oncology. It means the people I’ve worked with have been successful and productive and feel that the guidance that I have imparted has enhanced their ability to be effective as clinicians, researchers and teachers.
What made you first realize you wanted to become a mentor?
In academic medicine, there’s always been the adage “see one, do one, teach one.” There’s a culture of imparting what you know onto others — whether you’re a resident teaching a medical student or intern, an attending physician, or laboratory head. I was thrilled to have the opportunity to train graduate students as well as MD and PhD fellows from the start of my faculty career. The is great satisfaction in helping these trainees pass qualifier exams, defend a thesis, obtain their own research funding and become independent researchers. I maintain texting groups with many of my former trainees and I enjoy continuing to offer scientistic, career and sometimes personal advice. Through the ASH/EHA translational research training in Hematology program and other avenues, I have had the opportunity to impact on many other careers and at the same time learn from these talented hematologists. As a Division Chief and now Cancer Center Director, my goal has always been to build impactful programs for our patients by recruiting, retaining and advancing the best quality trainees and faculty. This requires an active approach, and I always think about ways to advance careers, whether it be by pointing out a new grant opportunity, a recent published paper, linking faculty and trainees or forging faculty collaborations. Mentorship means devoting a significant part of your own intellectual bandwidth to advance others. Mentorship also means developing careers of all who you work with, including other health care professionals, administrators, and research technologists.
What drove you to study hematology, and what event or lesson early in your career prepared you most for where you are today?
I would say that the reason that I am in the field of malignant hematology has much to do with inspiring mentors during my fellowship at Dana-Farber. From leaders like Ken Anderson, Jerry Ritz, Robert Mayer and George Canellos, I learned the natural history and treatment trajectories of these diseases. I formed tight bonds with many of my patients as a fellow and attending. I even had a patient with MDS/AML who I took care of as an intern, resident, fellow and instructor because of the relapsing nature of his disease. These patients, who underwent arduous medical treatments, remain as inspirations.
A combination of factors prepared my role in academic hematology/oncology. I think the experience of going through challenging training in medical school, residency and a medical oncology fellowship — and also spending an almost equal amount of time as I did in medical school as a postdoctoral fellow — then getting out of my area of comfort in medicine and learning new things in molecular biology, including taking graduate school classes, was all part of developing a large knowledge base.
My postdoctoral work was rigorous and led to my retraining as a molecular biologist focused on gene regulation but not on any one type of malignancy. My research into blood malignancies began in earnest began shortly after I joined the faculty of Mount Sinai in 1991 inspired by a hematologist who has become a mentor and guide to me for nearly 30 years: Samuel Waxman, M.D., a highly accomplished hematologist who was a pioneer in the concept of differentiation therapy for cancer, including retinoid acid for the treatment of acute promyelocytic leukemia. I interviewed with him when I joined the faculty at Mount Sinai in 1991. He knew my postdoctoral research on the study of the Drosophila Krüpple transcription factor and one day he called me up and said “We discovered a gene that’s involved in an unusual form of leukemia and it’s very similar to the fruit fly gene that you study. Would you like to work with us to investigate the relevance of this gene to the causation of this form of leukemia?”
That changed everything for me and was my entry to the field. We formed a collaboration including scientists in the UK and China and I joined a network of experts in the field. Together, we elucidated the function of PLZF a protein rearranged with the retinoic acid receptor in a rare and retinoic acid-resistant form acute promyelocytic leukemia.
What is your area of focus and what are your main research/clinical interests?
My area of focus for thirty years has been on abnormalities in the proteins that control transcription from DNA into RNA, the mechanisms of malfunction, the target genes that are mis-regulated and ways to reverse aberrant gene regulation and restore normal cellular growth. My lab has studied mutations of gene regulators in myeloid and lymphoid leukemia, lymphoma and most heavily over the past decade, multiple myeloma.
Within your area of expertise, what do you feel are the most exciting recent breakthroughs and biggest challenges?
I think one of the biggest breakthroughs that have occurred malignant hematology resulted from the widespread use of next generation sequencing to understand all of the genetic lesions and gene expression anomalies that stimulate the formation of blood cancers. With this cataloging, we now know the enemy. The problem is that, with many of these diseases, malignancy doesn’t develop in one pattern but results from dozens of combinations of mutations, chromosomal rearrangements, gene copy number changes and alterations of gene expression. Customized approaches have worked, notably the recent approval of inhibitors of mutant IDH1 and IDH2, but for many hematological malignancies there are not agents available to target the genetic lesions. The problem of tumor cell resilience and persistence in the face of targeted inhibitors, also threatens the success of novel treatments. The approvals of histone deacetylation inhibitors and EZH2 inhibitors offers hope to normalize gene expression patterns in blood cancer and ongoing research is exploring how to best utilize these drugs across genetically heterogenous diseases. Notably, increasing evidence shows that aberrant gene regulation in blood malignancy affects the ability of tumor cells to respond to immune attack, and there is increasing interest in combining epigenetic and immune therapy.
Who were your mentors, and what is the best advice they shared with you?
I think you first have to think about role models in your life who have inspired you to choose a career in medicine, science and investigation. People come to mind like Mr. Davies, my 6th grade science teacher who created a sense of wonder and discovery. My family physician, who advised I should think about a career in medicine to advance career in science with the ability to impact on patients and society.
Other inspirations were David Spriggs, MD, the chief resident who propelled me during my 4th year as a student at Columbia and later was one of my attendings at Dana-Farber. Barrett Rollins, M.D., Ph.D who as my senior resident at Beth Israel, brought together science and medicine at every morning rounds. Alan Rosmarin, MD another supervising resident and dear friend for 40 years was a year ahead of me in fellowship and molecular biology training and has always been a shining model of a physician, scientist and leader. Ben Neel, M.D., Ph.D., was my intern, but also a role model and inspiration due to his intellect and mastery of clinical and basic knowledge, now as Director of the Perlmutter Cancer Center at NYU. Karen Antman M.D., now Dean of the School of Medicine at Boston University was my clinical mentor while I was working in the field of soft tissue and bone sarcomas taught me the basics of clinical research. My laboratory mentor, Ulla Hansen, Ph.D., is a molecular biologist who taught me precision and to always questioning one’s own science and data to make sure results are rigorous and reliable. All of these mentors emphasized hard work, persistence, honesty and integrity.
What advice would you give to someone considering entering hematology?
Hematology challenges clinicians to be very astute about internal medicine since abnormalities of blood can affect virtually every organ. In terms of research, the ready availability of blood makes it relatively easy to do translational research. I also find the hematology community to be supportive, inviting and geared toward mentorship and excellence. I think that the best advice for the hematology trainees is to be persistent and optimistic and generous. You may have disappointments: patients who don’t do as well as you hoped, experimental ideas don’t work out, grants or papers receive rejections and need to be revised. But staying the course will lead to a lasting and fulfilling career. Giving some of your knowledge and wisdom to others multiplies your impact and yields enormous satisfaction.