Few scientists have a clearer view of where myeloproliferative neoplasm (MPN) research is headed than Dr. Ann Mullally, MD. As a physician-scientist, Division Chief of Hematology at Stanford, and member of the MPN Research Foundation’s Scientific Advisory Board (SAB), she sits at the crossroads of patient care, clinical trials, and discovery science.
From this vantage point, she shares her insights on the future of MPN therapies, technologies, and collaborations. But the story of how she reached this perspective begins with a bold decision she made more than a decade ago, when a new mutation had just been discovered.
Riding a research wave
In 2013, just months after opening her independent laboratory, Dr. Mullally found herself at the crest of a scientific wave. The discovery of mutations in the calreticulin (CALR) gene was poised to reshape the field of MPNs. In a bold move, Dr. Mullally immediately pivoted her research, shelving previous plans to focus on unraveling how CALR mutations redirect cellular mechanics.
MPN is a challenging group of malignancies where precise targeting is essential. “The body doesn’t tolerate eliminating normal blood stem cells,” said Dr. Mullally in a recent interview, “because then you have no blood production and then you can’t survive, right? It’s been more difficult to precisely target in the myeloid malignancies without hitting normal blood stem cells, but the discovery of CALR mutations has really changed that.”
By 2016, her laboratory, and others working in parallel, mapped the oncogenic mechanism of mutant CALR. Her decision to pivot helped establish herself as a central figure in MPN research and positioned her at the forefront of a rapidly changing field.
Building a career at the intersection of biology and the clinic
Like many other great researchers, Dr. Mullally’s career is inspired by insights from the clinic. “If I see a patient in the clinic and they have an outcome that I never would have predicted based on the biology of their disease, that triggers a question in my mind — why did that happen?” she explained. Those questions become hypotheses, tested in the laboratory using mouse models, cell lines, and increasingly, patient samples.
Her move to Stanford in 2024 expanded that translational loop. There, she’s close to the action, working closely with Stanford clinical trialists, Drs. Jason Gotlib and William Shomali who oversee a strong clinical program in MPN, with two therapies in phase 1 trials now enrolling patients:
Long anticipated by patients and researchers alike, these are first-in-human studies that directly target mutations that cause MPNs. “To actually have these patients enrolling on trials now is really exciting,” she beams, sitting in her new Stanford office.
Inside the SAB – a bird’s-eye view of the field
Alongside her laboratory and clinic work, Dr. Mullally plays a strategic role as a member of MPN Research Foundation’s SAB, which she joined in 2021. She describes the group as “very thoughtful, with diverse expertise, placing patients at the center of everything we consider and discuss.”
Those discussions give her a panoramic view of the field. She sees promising early-stage projects before they mature into published studies, and she participates in debates that help direct the Foundation’s resources toward the ideas most likely to make a difference for patients. For Dr. Mullally, the SAB is about good scientific practices; fostering healthy debate, mutual respect, and shared purpose.
Where the field is headed – Dr. Mullally’s predictions
With such a unique vantage point — deeply involved in patient care, guiding laboratory studies and shaping the strategies of MPN Research Foundation and Stanford Hematology — the future of MPN research begins to take shape.
- Mutation-targeted therapy: Dr. Mullally believes that mutation-specific therapies, like CALR antibodies and JAK2-selective inhibitors, will be most effective if introduced early in the disease course — when patients’ genetic profiles are relatively simple.
- Mutation-agnostic approaches: For advanced myelofibrosis, where patients often harbor 3 or more mutations, she argues that therapies must move beyond single genetic targets. “Targeting multiple proteins concurrently on the same cell, in a myeloid cell, may be a way that would give us specificity for the MPN stem cell that the normal blood stem cell would not have.” Multi-protein targeting in combination may also offer ways to overcome resistance.
- Focusing on rare cells: Advances in single-cell sequencing allow researchers to study rare stem and progenitor cell populations in unprecedented detail. Dr. Mullally expands on this, sharing “if you just study it as an aggregated population, you can really miss what’s happening in the most important cells. The ability to study single cells is very powerful and there’s been a lot of advances in that in recent years. And so that’s something we’re increasingly doing is studying primary human cells.”
- Artificial intelligence and virtual cells: AI is paying dividends on early investments in protein engineering & drug discovery. Looking further ahead, Dr. Mullally envisions “the generation of a virtual human cell,” also known as an in silico approach. “Synthetic cells generated on a computer (e.g. plus/minus an MPN causing mutation) can be perturbed in silico to determine impact of therapeutic interventions,” says Dr. Mullally.
“There has never been a more exciting time to be involved in blood cancer research.”
Looking back, looking forward
From riding the first wave of CALR discovery to guiding the field at Stanford and through MPN Research Foundation’s SAB, Dr. Mullally’s journey illustrates how pivotal decisions can shape a career. Dr. Mullally is one of the clearest voices on where MPN research is going next. With greater resources, she believes organizations like MPN Research Foundation could spearhead a global consortium for collaborative research — because, as she puts it, “MPN or cancer in general, does not recognize international borders and I think scientific research should operate similarly.”
That global perspective, combined with her daily engagement with both patients and trainees, keeps her focused on the larger mission: “We are all very vested in improving the care of patients with MPN,” she emphasizes.
Dr. Ann Mullally’s story is one of seizing opportunities at pivotal moments and keeping an eye fixed firmly on what comes next. From CALR biology to cutting-edge clinical trials, her career mirrors the trajectory of the field itself: driven by discovery, grounded in patient need, and always reaching for new discoveries.
