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Dr. Shannon Elf: CDP Special Fellow Achievement Award Winner

Anne-Marie Silvi and Erik Nelson
January 27, 2020

Dr. Shannon Elf, rising star in the blood cancer field, is a highly driven and compassionate investigator dedicated to the pursuit of new therapeutic strategies targeting the molecular dependencies of myeloid malignancies. With recent publications in Blood and Cancer Discovery, her research exhibits a high level of impact and cutting-edge developments, securing her place as a winner of the first annual LLS Career Development Program Achievement Award. This award, given to one investigator in each category of the Career Development Program (CDP), recognizes the achievements of awardees of this program who have made great strides in their careers over their award periods. Dr. Elf was awarded in the Special Fellow category and received a reward of $10,000, which she plans to use to continue her impactful research.

Dr. Elf has always held an affinity for the natural world. Having grown up in Sandy Hook, CT, she expresses fond memories of time spent gardening with her mother and walking through the woods with her father. At a young age, she developed a deep love of animals, with an emphasis on sea creatures. Her passion for ocean life drove her to enroll in biology in her sophomore year of high school, a full year ahead of her peers. It was in this class that she discovered her fascination with the inner workings of the cell, leading to her eventual professional focus on molecular biology.

Dr. Elf’s selection of Bowdoin College as her undergraduate school was driven by her desire to pursue a career in biology while continuing to nurture her other passions of language and music. At Bowdoin, she completed a double-major in biology and music with a minor in English, and to this day, she values the strong critical thinking and writing skills that she retains from her well-rounded education. About halfway through her undergraduate experience, Dr. Elf lost a friend to acute myeloid leukemia (AML). She was struck by the rapidity with which the disease stole the life of her friend, whom she remembered as a healthy, active individual with a world of opportunity ahead of him. This devastating loss was the initial inspiration that prompted her interest in leukemia and cancer in general.

In Dr. Elf’s senior year at Bowdoin, she took an immunology course that ignited her fascination with blood. She recalls the first reading assignment from this class – Immunology by Emil Von Behring and Kitasato Shibasaburō (1890). The description of blood in this paper, which Dr. Elf remembers as a “mystifying reservoir of ‘substances’ that had seemingly magical properties,” evoked the familiar feelings of mystery and intrigue that her younger self had felt for the ocean. It was this description that solidified Dr. Elf’s certainty that she would dedicate her career to the study of blood.

The next few years of Dr. Elf’s journey, between undergraduate and graduate school, introduced her to several life-long mentors. After graduating from Bowdoin, she worked as a technician in the laboratory of Daniel Tenen at Harvard. She was drawn to the diverse backgrounds of the scientists in his laboratory, and she learned a great deal from Dr. Tenen, including the importance of having “strong scientific opinions and principles” to guide her. In addition to Dr. Tenen, the post-docs in his laboratory at that time – Gang Huang in particular – became important influences in Dr. Elf’s life. When Dr. Elf’s father was diagnosed with small cell lung cancer in her last year in the Tenen lab, Dr. Huang suggested that she seek a technician position in Steve Nimer’s laboratory at Memorial Sloan Kettering Cancer Center in New York City, where he was moving to complete his postdoctoral training. This new location allowed her to live at home, and though the commute was challenging, she was (and will forever be) grateful to have been able to see her father every day of that last year of his life. It was during this very challenging stage of her life – both emotionally and physically with a five-hour daily commute – that she learned the important lesson from Dr. Nimer that her career of choice is a marathon rather than a sprint. She resolved to not overwork herself and to trust that she would reach her goals in due time. Her father lost his battle with cancer shortly before Dr. Elf began graduate school, and his memory will forever be her motivation in her career fight against what she calls the “devastating monster that is cancer.”

In researching graduate programs, Dr. Elf took an extremely methodical approach, seeking schools with laboratories in her particular area of interest. Specifically, she was interested in signaling in myeloid leukemias – at the time a logical complement to her prior laboratory experience in transcriptional regulation in myeloid leukemias. She selected the Molecular & Systems Pharmacology program at Emory University Winship Cancer Institute, where she joined Jing Chen’s laboratory, which well suited her interest.  After studying tyrosine kinase signaling in leukemia for her first three years in graduate school, Dr. Elf transitioned the focus of her PhD to the study of cancer cell metabolism in leukemia. This was a fairly new area of study, giving her the opportunity to seek novel targets with the potential to aid in the discovery and development of new therapies that give patients a break from chemotherapy. In addition, her time in this laboratory allowed her to develop a friendship and mentorship with Dr. Chen who trained her to become a “stringent, meticulous, self-critical experimentalist” and taught her how to form narratives from data collected in the laboratory and who, incidentally, became an LLS Scholar within this same period.

While Dr. Elf worked in the Chen lab, she also received mentorship from Sumin Kang, whom Dr. Elf, as a graduate student, idolized and hoped to emulate in her own career. Dr. Kang recounts that though Dr. Elf was her mentee, “there were more things I learned from her in all aspects during her stay in Emory.” The day that Dr. Elf’s mentor Sumin Kang received notice of her Scholar award from LLS is one that Dr. Elf holds fondly in her memory of her time at Emory University. The whole laboratory celebrated Kang’s accomplishment, and Dr. Elf determined then and there that she would follow in Dr. Kang’s footsteps. Last year’s transition to an independent position moves her one step closer to receiving the LLS Scholar award, to which she aspires.

Sumin Kang and others who have worked with Dr. Elf note the exceptional passion Dr. Elf has for her work. This passion shines through in the way she describes her experience in Jing Chen’s laboratory. The laboratory was located in the same building as clinical offices where patients with cancer are treated. Every day, Dr. Elf encountered the faces of patients undergoing chemotherapy – faces that reminded her of her father in his last days and made apparent the pain inherent to life with cancer. She remembers this experience as a daily lesson in perseverance, noting that however long or difficult her day in the lab, it could never compare to the battle these patients faced. Her compassion carries through in her consideration of the patient samples used in her experiments, always aware that there is a person behind each sample who made a sacrifice in order to provide it. This attitude was reinforced when she had the challenging but valuable opportunity one day to witness a bone marrow biopsy – a very unpleasant and often painful procedure – performed on a young man to collect a sample for her experiment. She vowed never to let a single drop of each precious sample go to waste.

After completing her PhD at Emory, Dr. Elf returned to Boston to work in the laboratory of Ann Mullally (now an LLS Scholar) at Brigham and Women’s Hospital. She was excited by the opportunity to dive into the study of myeloproliferative neoplasms (MPN), which was completely new to her. Just as she was getting started in this laboratory, there was a major breakthrough in this disease category: Calreticulin (CALR) was found to be mutated in approximately 40% of MPN patients. Dr. Mullally entrusted Dr. Elf with the task of dissecting the molecular mechanism of this newly-discovered mutation. Since CALR was not known to be mutated in any other cancer, it was a mystery how mutations in this protein were associated with the development of two types of MPNs: essential thrombocythemia (ET) and primary myelofibrosis (MF). Dr. Elf’s research demonstrates that mutant CALR is sufficient to cause MPN in cancer models and that mutant CALR requires an interaction with the MPL receptor in order to be oncogenic. This interaction may provide an explanation as to why mutant CALR affects ET and MF but not polycythemia vera, another MPN that, unlike ET and MF, does not have MPL mutations.  Her research further demonstrates that the specific amino acids mutated in CALR appeared to be less important than the changing of one end of the protein from a negative to a positive charge. This is a novel mechanism of action for an oncogene and may relate to the interaction of mutated CALR with MPL – an interaction that does not happen with unmutated CALR. This highly impactful work was one major factor that earned Dr. Elf her position as an independent investigator.

Dr. Elf cherished the freedom she had under Ann Mullally’s leadership to grow toward independence. Dr. Mullally gave her the freedom and confidence to take ownership of the direction of her experiments and trusted her to follow her scientific instincts. Benjamin Ebert, who had just recently been a mentor to Dr. Mullally prior to her transition to an independent position, also served as a mentor to Dr. Elf. She describes them both as “down to earth, kind, and funny” and, perhaps most importantly, very approachable. She values the opportunity she had to develop as a scientist in this laboratory, in an environment that fostered her confidence and independent thinking. At the same time, Dr. Elf mentored several students and postdoctoral fellows who passed through the laboratory, an experience she found highly rewarding.

Last year, after five years as a postdoc in the Mullally laboratory, Dr. Elf was hired as an assistant professor to lead her own laboratory at the Ben May Department of Cancer Research at The University of Chicago. Head of this center, Michelle Le Beau, is enthusiastic about the research being pioneered by Dr. Elf’s laboratory, which she notes “has tremendous promise for the identification of targeted therapies for the treatment of myeloid malignancies.” Since opening her lab, Dr. Elf has grown her team rapidly and now leads eight students, from undergraduate to graduate and medical school, one postdoc, and two technicians. Depicted below are some of the members of Dr. Elf's lab:​ 

Following the example set for her by her mentors, Dr. Elf strives to provide her team with an encouraging, positive environment where they can learn freely. Her laboratory expands upon her important discoveries about mutant ​CALR in MPNs by focusing on other pathways that may be affected by this mutation. Unmutated CALR functions in part to mediate the unfolded protein response (UPR), which is a mechanism by which the cell deals with improperly processed proteins to aid in cellular survival. Cancer cells often coopt the UPR to aid in their own survival. Dr. Elf hypothesizes that MPN cells may do this by using mutant CALR– a hypothesis that she is pursuing in her new laboratory. This research may lead to new ways to treat MPNs, which are diseases with no known cure.

The Leukemia & Lymphoma Society is proud to support Dr. Elf’s career development as she conducts cutting-edge research in MPNs. Jing Chen calls Dr. Elf “a wonderful example of the talented and passionate young investigators to transform leukemia care with their groundbreaking science.” Ann Mullally also comments on Dr. Elf’s exceptional abilities, especially noting her outstanding scientific intellect to thoughtfully develop a series of key experiments to test a hypothesis. She is confident that Dr. Elf “will no doubt continue to make important contributions to the hematological malignancies field.” We congratulate Dr. Elf on her outstanding accomplishments and look forward to seeing the exciting new developments she will doubtlessly bring forth as an independent investigator.

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