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Cheryl Willman, M.D. — 2015 STC.UNM Innovation Fellow

2015bDr. Cheryl L. Willman, recipient of the 2015 STC.UNM Innovation Fellow Award, is a healer and an innovator. As a researcher and clinician, she is witness to the pain and suffering of cancer and powerfully committed to the quest to find cures. Trained as a pathologist at the Mayo Medical School, Dr. Willman is a cancer biologist who studies the genetic make-up of leukemias, and uses the tools of genomics to understand and discover underlying mutations in leukemia cells. By understanding cell behavior through single cell and single molecule biology, she hopes to develop better treatments for cancer patients.

There are no better words than those of Dr. Paul Roth, Chancellor for UNM Health Sciences and Dean of the School of Medicine, to summarize Dr. Willman’s achievements.

“Cheryl Willman is a visionary leader, care provider and innovator who, throughout her illustrious career, has made immeasurable contributions to the health and well-being of all New Mexicans.

Dr. Willman was appointed director and CEO of the University of New Mexico Cancer Center in November 1999. Under her stewardship, the Cancer Center was first awarded a five-year National Cancer Institute P20 Cancer Center Planning Grant in 2000. Five years later, the Center succeeded on its first attempt at NCI Designation and was awarded a NCI P30 CCSG grant. The Center underwent a highly successful competitive renewal in 2010 and is undergoing another renewal this year. As a clinical enterprise, the Cancer Center has been a stunning success: it serves 60 percent of the adult and virtually all of the pediatric oncology patients in New Mexico.

Dr. Willman is also an internationally recognized physician scientist. She has for more than 30 years been continuously funded by NIH, NCI, LLS and private foundations. Her career has been devoted to fundamental, translational and clinical cancer research, primarily in leukemia.”

Dr. Willman’s research group focuses mainly on characterizing and targeting therapies for leukemia. The researchers look at gene expression patterns and underlying genetic events to identify groups of patients with targetable characteristics. By taking advantage of the specific features of these expression groups, it is possible to develop focused therapies to treat these patients with maximum efficacy and minimal side effects. Over the past several years, this discovery effort has branched over into targeted therapeutics as well. In conjunction with UNM and Sandia Lab colleagues the group is now exploring the application of nanotechnology as a way to deliver anti-cancer drugs to tumors. The discoveries stemming from these efforts will likely be applicable to many other cancers.

Acute lymphoblastic leukemia (ALL) is a cancer of white blood cells, the cells in the body that normally fight infection. It is the most common cancer in children. Over the last several decades, advances in the treatment and supportive care of pediatric ALL have dramatically increased its five-year survival rate from 80 to 85 percent. Despite these improvements, a considerable number of children with ALL continue to relapse following standardized treatment. Accurately diagnosing those patients who are high-risk for relapse and treating them with targeted therapies may greatly enhance their outcomes.

Dr. Willman and her research group have been studying Hispanic and Native American children with ALL who have a very poor response to standard therapies and low survival rates (30 to 50 percent). Using next-generation genetic sequencing to identify active genes in cancer cells, the researchers discovered that these children have a particular form of leukemia called Philadelphia-like (Ph-like) ALL, caused by a genetic mutation (also affecting adult ALL patients) that non-Hispanic and non-Native American children do not have. The research has been done in collaboration with St. Jude Children’s Research Hospital, National Cancer Institute (NCI) and the Children’s Oncology Group. Several new therapeutic targets and diagnostics have resulted from this research that are being tested in clinical trials. The new discoveries have led to several patents and pending patents at the UNM Cancer Center. The Cancer Center just received FDA approval for a new diagnostic that it will use to conduct a national study of 4,000 leukemia patients this year using genetic sequencing to search for the mutations associated with Ph-like ALL that can be the targets for newly discovered existing cancer drugs that are effective against these mutations, leading to new clinical trials.

Dr. Willman’s work with Dr. Jeff Brinker, from the UNM School of Engineering and Sandia Labs, on developing nanoparticle technologies holds great promise for better cancer therapeutics. Cancer research and treatment today is centered around finding genetic mutations in cancer cells and finding or developing drugs that target the mutation. It will require genomic technologies, modeling tools, nanotherapeutics and nanoparticles to revolutionize treatment. It is a two-pronged approach of having the right drug and the right delivery system going directly to the cancer cell that will be crucial to successful treatment.

In 2010, a collaboration among UNM and Sandia, led by Dr. Brinker, and the UNM Cancer Center, led by Dr. Willman, coalesced into a $6 million funding partnership with the NCI Alliance for Nanotechnology in Cancer and the state of New Mexico. One NCI grant established a UNM Cancer Center/ UNM/Sandia joint cancer nanotechnology program and another one created a new cancer nanotechnology training program to train a new generation of multidisciplinary engineers, life scientists and oncologists. The state funded a new lab supporting Dr. Brinker’s research into nano-bio materials and nanomedicine in space donated by the UNM School of Engineering at its Centennial Engineering Center. The development of the protocell technology is the amazing result of this effort to develop new and innovative cancer diagnosis and treatment methods by using nanotechnology.

The protocell technology, essentially a cell replica, consists of a silica nanoparticle about 150 nanometers in diameter (the size of a virus) and a lipid bilayer. It has cavities like a honeycomb that can store large amounts and varieties of drugs (a 1,000 times greater dosage than liposome carriers). Silica’s binding ability also contributes to keeping the cargo stable. The nanoparticle is encapsulated by the lipid bilayer (a liposome), a hydrophobic, cell-like membrane, that seals in the drugs until the protocell is within the cancer cell. The lipid bilayer also carries the particular ligand (molecule) that binds to the targeted receptor molecule overexpressed on the cancer cell, allowing the protocell to penetrate the cancer cell and kill it while leaving normal cells alone. The protocell technology is designed, through an elegant gating method, to release its cargo once it’s inside the cancer cell. The protocell technology led to the creation of STC start-up Alpine Biosciences, Inc. (recently acquired by Oncothyreon).

The collaboration continues. Dr. Brinker and Dr. Willman and their research groups are working together to test the protocells efficacy, viability, and toxicity in animal studies and clinical trials, including drugs identified by Dr. Willman as being effective against acute lymphoblastic leukemia. The protocell is being developed for treating other cancers as well.

Dr. Willman and the UNM Cancer Center’s latest research collaboration with five other U.S. cancer centers will focus on pooling genetic data on cancer tumors to more rapidly match patients with treatments and drug clinical trials. This is of tremendous value to New Mexico and other small population states where the number of patients is also small. The research collaborative, called the Oncology Research Information Exchange Network, or ORIEN, is focused on advancing understanding of cancer at the molecular level in order to develop targeted cancer treatments. By sharing data among its many member institutions, ORIEN hopes to not only more quickly match patients to a greater number of clinical trials but to accelerate the development of new treatments as well. UNM’s protocell technology is a perfect example of a complementary technology which could be the breakthrough delivery system that brings these new targeting drugs to the cancer cells. Other ORIEN member include the Moffitt Cancer Center, Ohio State University Comprehensive Cancer Center, City of Hope, University of Virginia Cancer Center, and University of Colorado Cancer Center.

Soon the ORIEN group will allow patients to enroll in a study that will completely sequence their cancers to be stored in a database. This too will help institutions find patients who have similar mutations and match them to suitable treatments and clinical trials.

The Cancer Center’s mission is to make sure that all New Mexicans have access to the Center’s world-class care and benefit from new treatments resulting from its innovative research to discover the causes and cures for cancer. The Center’s outreach programs in Las Cruces, Santa Fe, Alamogordo, and Farmington are serving New Mexicans in urban, rural and tribal communities who do not have access to the best cancer treatment and care the state has to offer. To carry out this work and sustain the mission, Dr. Willman and her outstanding team of cancer doctors and researchers are also educating the next generation of cancer healthcare professionals. Dr. Willman has said that she has a passion for large projects, a belief in a career of service, and a dedication to doing the very best science possible. Building a cancer center facility and program that is patient focused and devoted to providing the full spectrum of care that every cancer patient needs, that is open to every patient in the state regardless of circumstance or background so that each receives the very best innovative treatments is a truly visionary achievement.

The STC.UNM Board of Directors is honored to present the 2015 Innovation Fellow Award to Dr. Cheryl Willman.