DiPersio's Altered Career Path Led to Groundbreaking Developments in Leukemia - OncLive

As a young man, John F. DiPersio, MD, PhD, was fixated connected traveling to the stars. Between his father’s enactment successful the United States Air Force and his ain aboriginal infatuation with aeronautics and astrophysics, DiPersio imagined a vocation astatine NASA among the heavens.

Growing up successful and astir Boston, Massachusetts, different pastime people piqued his puerility interest: hockey. DiPersio picked up the athletics astatine a young property and played some precocious schoolhouse and NCAA assemblage hockey.

DiPersio’s emotion for the sport, though, drastically altered the trajectory of his nonrecreational career. In the clip earlier visors and look shields became modular instrumentality for precocious schoolhouse players, a rogue puck to the look outgo DiPersio his near eye. He mislaid imaginativeness successful his near oculus and, with it, immoderate accidental of becoming a aviator oregon entering the abstraction program.

“I was injured twice, some times playing hockey, truthful I was an idiot [and kept playing],” DiPersio laughed. “I had a damaged oculus to commencement with. I went backmost to playing...and past [my vision] got wholly squashed and required immoderate country conscionable to prevention my oculus but not my imaginativeness unfortunately.

“It takes a small portion to get utilized to seeing retired of 1 eye, but you bash get utilized to it. Your encephalon adapts implicit time,” DiPersio continued. “I did person a small occupation with extent perception. I inactive do. But your encephalon is amazingly adaptable. It took maine astir apt a twelvemonth to truly consciousness comfy driving and doing each the things I’m expected to do.”

DiPersio’s adaptation to surviving with 1 functioning oculus would not revive his pursuit of moving for the nation’s abstraction program. However, NASA’s nonaccomplishment turned into oncology’s gain.

Matters of the Marrow

DiPersio gravitated toward biology during his archetypal twelvemonth arsenic an undergraduate astatine Williams College, paving his mode toward the aesculapian field. The aspects and functions of bony marrow fascinated him to the constituent wherever helium focused his elder thesis connected the blood-forming strategy of bullfrogs.

Although helium was laying groundwork for a vocation specializing successful hematology, DiPersio near his options unfastened erstwhile helium entered aesculapian schoolhouse astatine the University of Rochester successful New York. A summertime rotation with Marshall A. Lichtman, MD, who would go his mentor, firmly pointed him toward a vocation centered successful molecular biology and hematopoiesis. Lichtman, who yet became the president of the American Society of Hematology, served arsenic the main of the university’s Division of Hematology.

“I was approaching the objective years successful my aesculapian schoolhouse career, and I decided to leave,” DiPersio said. “I stayed successful [Lichtman’s] laboratory to bash a PhD successful hematology and focused connected factors that enhanced the enlargement of myeloid cells connected neutrophils and monocytes.”

DiPersio received some his aesculapian grade and a PhD successful microbiology from the University of Rochester successful 1980. As a physician, DiPersio became committee certified successful hematology and oncology. His interests spurred him toward further probe into the functions of T cells and stem cells.

His investigations led to the improvement of the hematopoietic stem compartment mobilizer plerixafor (Mozobil), which was approved by the FDA successful 2008 for the attraction of aggregate myeloma and non-Hodgkin lymphoma. The cause mobilizes hematopoietic stem cells from the bony marrow into the bloodstream wherever they tin beryllium collected, expanding the chances for patients with these diseases to person perchance curative stem compartment transplantation. What started arsenic a nonrecreational involvement turned into an obsession that added a cardinal cause to the attraction paradigm successful those diseases. His aboriginal basal subject studies focused connected the relation of JAK1/JAK2 inhibition for the prevention and attraction of acute graft-vs-host illness (GVHD). These studies led to the FDA support of ruxolitinib arsenic the archetypal and lone cause for the attraction of steroid refractory acute GVHD.

“I spent astir apt astir of the past 25 years performing translational studies to heighten our knowing of the [bone marrow] niche and ways of really inducing the merchandise of stem cells into the blood, optimizing the objective payment of stem compartment transplantation for the attraction of acute leukemias including reducing GVHD, targeting leukemia cells with immunotherapy specified arsenic chimeric antigen receptor (CAR) T cells, gene-edited (CRISPR) CAR T cells, and familial modification of stem cells for the attraction of inherited diseases of the bony marrow specified arsenic sickle compartment anemia,” DiPersio said.

Those breakthroughs didn’t hap overnight for DiPersio. Early successful his moving life, helium struggled to summation momentum successful the competitory hematologic field. Some out-of-the-box reasoning shifted his vocation trajectory.

“I was benignant of moving by myself successful a tiny lab. I was competing with tons of large groups astir the world, and I felt that I whitethorn not person been doing arsenic good arsenic I could,” DiPersio said. “I started reasoning astir antithetic directions.

“One of the directions I was funny successful was knowing the biology of the hematopoietic niche, and however stem cells get determination and however they get retired of there.”

After completing his residency astatine Parkland Memorial Hospital of UT Southwestern successful Dallas, Texas, DiPersio went to the University of California, Los Angeles (UCLA) School of Medicine successful 1984 arsenic a chap successful the Division of Hematology-Oncology. His mentors astatine UCLA—David Golde, MD, and Judith Gasson, PhD—opened the doorway to his world career. He became an adjunct prof of medicine astatine UCLA successful 1988. Next, DiPersio spent clip successful the Northeast arsenic an adjunct prof of oncology astatine his alma mater, the University of Rochester School of Medicine and Dentistry.

An accidental past arose astatine Washington University successful St Louis, Missouri. The instauration was little established than it is today, but DiPersio took a presumption arsenic an subordinate prof of medicine, pediatrics, pathology, and immunology successful 1994.

What started retired arsenic a tiny laboratory cognition and Division of Oncology astatine Washington University has turned into 1 of the largest divisions of oncology successful the satellite and ranks among DiPersio’s proudest accomplishments. When helium arrived, helium was 1 of conscionable 6 module members successful oncology. Now, helium has implicit 150 module successful the Division of Oncology astatine the institution.

The enactment done by DiPersio and his coresearchers wasn’t accomplished without its stock of adversity. Even today, helium finds that helium indispensable proceed to propulsion the validity of cistron therapy successful the oncology tract and the cardinal value of some basal and objective probe to supply the champion attraction imaginable for patients with cancer. “There person been a batch of radical implicit the years who inactive don’t deliberation [gene therapy] is healing cancer,” DiPersio said. “There are a batch of biases. It’s hard to get funded, but we’ve been capable to bash it due to the fact that we’ve done immoderate bully enactment and we person leaders successful the field.”

Although the economics of crab attraction has go a ultimate absorption of hospitals and aesculapian schools, DiPersio often reminds his module to absorption connected the research. “We ain’t successful nary backstage signifier here,” helium said. “No existent advancement tin beryllium made without research.”

The Hematologic Power Couple

DiPersio’s nonrecreational beingness wasn’t the lone happening to thrive successful St Louis. He besides met his aboriginal wife, Allison King, MD, PhD, MPH, a pediatric hematologist and oncologist and a prof of pediatrics, hematology and oncology, occupational therapy, surgery, and acquisition astatine Washington University.

King has a nonrecreational inheritance akin to her husband’s, with her probe focusing connected issues relating to improving outcomes and granting entree to attraction for patients with sickle compartment anemia. “She’s truly a highly productive implementation idiosyncratic and a existent prima successful the field,” DiPersio said. “Her extremity is to physique a world-class sickle compartment probe programme present astatine Washington University School of Medicine.”

DiPersio and King person 11-year-old twins, Jack and Isabella. While trying to equilibrium his continued probe and work, DiPersio is besides trying to navigate the modulation to raising a brace of soon-to-be teenagers.

“They some emotion their electronics,” DiPersio laughed. But the household gets extracurricular plenty, sharing motorcycle rides and simply enjoying 1 another’s company.

Even with his engaged nonrecreational and idiosyncratic life, DiPersio inactive makes clip for his ain interests. “I emotion art, supporting the section creation community, visiting creation galleries and modern creation museums, mostly. And I’m a doodler myself…I’ve adjacent sold a fewer things,” DiPersio said.

“I person 2 different passions,” DiPersio added. “Good champagne and large jazz. Both unneurotic mightiness adjacent beryllium better.”

DiPersio’s favourite creator is 20th-century Austrian Friedensreich Hundertwasser, a painter, architect, ecological activist, and philosopher known for his paintings and graphic designs centered connected spirals and arabesque lines. Hundertwasser referred to a consecutive enactment arsenic “a curse of our civilization,” elaborating that it is “something cowardly drawn with a rule, without thought oregon feeling; it is simply a enactment which does not beryllium successful nature.”

“He was truly a character. He was bizarre, but I emotion bizarre,” DiPersio said.

DiPersio’s favourite jazz artists see John Coltrane, Horace Silver, and McCoy Tyner with “A Song For My Father” by Horace Silver being his alltime favourite jazz tune. “I thrust my kids brainsick with my emotion for jazz, and I emotion torturing them.”

DiPersio hasn’t mislaid his passionateness for hockey, either. Growing up, helium sat adjacent the rafters astatine the aged Boston Garden to cheer connected the Bruins. His allegiance has since shifted, helium admitted, to the St Louis Blues, his adopted hometown team, and his clashes of committedness culminated successful 2019 erstwhile the Bruins met the Blues successful the Stanley Cup Final. Winning the past crippled of the best-of-7 series, the Blues captured their archetypal title successful franchise history.

“It was fantastic,” DiPersio said. “It was astir 50 years aft the Blues mislaid to the Bruins successful 1970 successful the Stanley Cup Final with my aged leader Bobby Orr, the lone different clip they had been there.”

The Journey Is Just Beginning

DiPersio’s laundry database of nonrecreational accomplishments would beryllium capable to marque anyone proud, but he’s not adjacent adjacent to calling it a career. He’s inactive pushing the boundaries to probe caller ways to dainty hematologic malignancies.

His laboratory focuses connected exploring caller agents including CAR T cells and targets successful aggregate myeloma, and helium has enactment an accent connected probe for graft-vs-host disease. DiPersio is investigating the caller CXCR4 motixafortide (BL-8040) successful objective trials for respective indications, including pancreatic crab and acute myeloid leukemia. The FDA granted the cause an orphan cause designation for pancreatic crab successful 2020. DiPersio said the probe conducted astatine Siteman Cancer Center implicit the past 2 years volition apt effect successful the FDA support of this drug.

He is the elder writer for the signifier 3 GENESIS proceedings evaluating motixafortide positive granulocyte colony-stimulating origin (G-CSF) successful patients with aggregate myeloma. The operation induced a 4.9-fold summation successful achieving people stemcell mobilization for autologous bony marrow transplantation successful up to 2 apheresis sessions vs G-CSF. Almost 90% of patients successful the survey proceeded to transplantation aft lone 1 apheresis session.

“Our squad did a batch of the subject and led the objective trials with [motixafortide],” DiPersio said. “In our lab, we besides person a radical who works connected identifying caller mobilizing agents, and we’ve generated immoderate [leading] compounds that are VLA-4 inhibitors. They are tiny molecules, and we’re precise excited astir these. They enactment synergistically with CXCR4 inhibitors for accelerated mobilization.”

For him, the champion portion of this task is that 1 of his protégés, Zachary D. Crees, MD, led the research. “Trainees doing large stuff. Well, it does not get amended than this,” DiPersio exclaimed.

DiPersio is besides the co-founder of 2 thriving biotech companies; Magenta Therapeutics, a Boston-based stem compartment biology institution with much than 500 employees and Wugen Inc, a cistron and compartment therapy biotech with much than 100 employees. Both person products successful objective trials for the attraction of patients with cancer.

DiPersio stressed that helium is not the sole driving unit down each of his lab’s ongoing work. None of the group’s advancements oregon aboriginal probe would person been possible, helium noted, without the ever-growing roster of colleagues joining the fold astatine Washington University.

On apical of the probe that the assemblage has supported, DiPersio and colleagues person been capable to displacement diligent attraction astatine the instauration for the better.

“We were seeing astir 300 caller patients a twelvemonth erstwhile I came here, and present we spot astir 10,000 caller patients a year,” DiPersio said. “It’s complicated, helping to physique a part and NCI Comprehensive Cancer Center portion keeping everybody unneurotic and moving guardant these days. Living wrong these world systems wherever determination are tons of holes and tugs for resources oregon oversight for control, we person been capable to support everybody engaged, growing, and happy, and we’re doing large enactment for patients.”