Dr. Hilda Ye

Dr. Hilda Ye

Drawn to the field of lymphoma by a fascination with the immune system and diseases caused by abnormal immune responses, Dr. Ye completed her PhD at the University of Kansas and her Postdoctoral training under the guidance of LRF SAB member, Dr. Riccardo Dalla-Favera at Columbia Medical Center. It was during her postdoctoral training at Columbia that Dr. Ye successfully cloned the BCL6 gene, a discovery that subsequently triggered a number of important studies in the B cell field as well as the lymphoma field.

Today, Dr. Hilda Ye is an Associate Professor in the Department of Cell Biology, Albert Einstein College of Medicine and a member of the Lymphoma Research Foundation's Panel of Scientific Advisors. Her research focuses on the molecular pathogenesis (the mechanism by which the disease is caused) of B cell lymphomas with a major emphasis on diffuse large B cell lymphomas (DLBCL), the most common type of aggressive lymphoma in the adult population.

"While we still lack cures for some of the common types of lymphomas, we are making significant inroads to the inner workings of these tumors and are starting to discover their Achilles' Heels."

Throughout her research, Dr. Ye's ultimate goal is to "apply the knowledge gained during basic and translational research to improve lymphoma prognostics and therapeutics." Dr. Ye explains that "similar to other kinds of B cell lymphomas, DLBCL derives from the so-called germinal center (GC) B cells found in secondary lymphoid organs." In line with this, Dr. Ye and her colleagues hypothesize that "the key characteristics of DLBCL, including cell proliferation and survival control, responsiveness to cytokines and stress stimuli, and genome maintenance capability, etc., are not only determined by the disease-specific oncogenes (a gene that has the potential to cause cancer) and tumor suppressors, but are also heavily influenced by the immunological and genetic characteristics of their cell-of-origin, the GC B cells. As such, although we always keep lymphoma-related questions in mind, our work straddles both normal GC B cells and B cell lymphomas. For example, we recently discovered that, in contrast to other types of B cells, GC B cells have a unique requirement for a cell cycle regulator called Cyclin D3, and that its function cannot be substituted by other members of the D-Cyclin family." Dr. Ye adds that "shortly after our study, mutations activating the Cyclin D3 gene were reported in a high percentage of lymphoma cases by Dr. Louis Staudt and colleagues in a Nature paper."

Emphasizing the often unintended findings and discoveries that are part of the nature of research, Dr. Ye recalls another example when "we were initially on a track to examine the influence of BCL6, the oncogene most frequently dysregulated in DLBCL, on cell signaling events downstream of IL-6." However, during the course of their work, they "unexpectedly found that BCL6 suppresses STAT3, another oncogene known to be involved in solid tumors and multiple myelomas." This finding subsequently triggered a series of studies aimed at defining the role of STAT3 in normal B cell differentiation, lymphoma transformation, as well as DLBCL prognosis and therapeutic response.

Reflecting on the changes that have occurred in lymphoma research in the past decade or so, Dr. Ye explains that "we and other researchers in the field have started to take a more holistic approach. We not only strive to find out how the tumor cells sustain themselves in vivo and how we can eradicate them more effectively, but also take into account the history of the precancerous cells, and ask what remains the same and what has changed after the malignant transformation step." Dr. Ye also recognizes an increasing emphasis on translational research, and feels that "the previously well-defined boundary between basic and clinical research is blurring." In addition, she comments "lymphoma research has benefited and will continue to benefit tremendously from technological advances in immunology, animal models, high-throughput genomics, drug design and development platforms." In her opinion, these exciting developments are paving the way for lymphoma-specific, targeted therapies, which will eventually lead to greatly improved quality of life and long-term survival.

In terms of developments on the clinical side, Dr. Ye acknowledges "while we still lack cures for some of the common types of lymphomas, we are making significant inroads to the inner workings of these tumors and are starting to discover their Achilles' Heels." So what are the potential implications of these advances for the modern lymphoma patient? As more academic physicians enter the hematology/oncology specialty, lymphoma patients today "will be cared for by doctors who are more knowledgeable about the disease mechanism and the newest developments in lymphoma therapeutics. The patient can also expect that important questions arising from the bedside will be addressed in a real-time manner in high performance research laboratories." As a result, "risk-stratified therapy and combinations of traditional treatment with new, targeted agents will gradually become the new norm."

As a member of the LRF Panel of Scientific Advisors, Dr. Ye says that "for me, the LRF SAB and grant review meetings are always an interesting and rewarding experience. These events facilitate networking with collaborators, keep me up to date with new trends in the field, and increase awareness of various issues and concerns on the mind of clinicians and other investigators in the lymphoma field."

Dr. Ye's three pieces of advice for researchers starting out in their career:

  • Surround yourself with wise people, and know when to seek advice;
  • Follow your passion but learn when it is time to drop your hypothesis;
  • The time of big science has come to cancer research, but there are still plenty of opportunities to win with a good idea.

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