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The Cancer Letter – Ned Sharpless, Trump’s choice for NCI director, described as erudite scientist whose expertise spans basic, clinical research

The Cancer Letter – Ned Sharpless, Trump’s choice for NCI director, described as erudite scientist whose expertise spans basic, clinical research

President Donald Trump announced his intention to name Norman “Ned” Sharpless to serve as the next NCI director. The appointment was announced late on June 9.


Sharpless, director of the UNC Lineberger Comprehensive Cancer Center and the Wellcome Distinguished Professor in Cancer Research, will replace Douglas Lowy, who has served as acting director at the institute since Harold Varmus stepped down as director in March 2015.


The position doesn’t require confirmation by the U.S. Senate. It’s not publicly known when Sharpless would be moving to Washington.


The decision to appoint Sharpless, a scientist and cancer center director, came three days after Trump appointed Francis Collins to head NIH.


Sharpless, 50, is described by colleagues as a solid, mainstream choice, which—in an optimistic interpretation—suggests continuity for the institute.


His experience includes laboratory science, a clinical practice, running a major cancer center, and starting two biotechnology companies, one of which recently went public. His interests also include Big Data projects. He is involved in developing cancer applications for IBM Watson.


“He was in my lab, at which time I predicted he would ascend to impactful positions based on a diverse array of his attributes of caring, integrity, entrepreneurial nature, drive, inquisitiveness, smarts, interpersonal skills and communication abilities,” said Ronald DePinho, a professor of cancer biology at MD Anderson Cancer Center and that institution’s former president.


Sharpless, who graduated from UNC and its medical school, did his internship and fellowship and later practiced at Harvard-affiliated institutions and worked at DePinho’s lab.


“Ned is a top-tier scientist contributing to our fundamental work in stem cells and cancer,” DePinho said to The Cancer Letter. “He is a skilled heme-onc physician who understands the need to translate discoveries into clinical advances that make a difference for cancer patients. His experience in creating biotech companies as well as running a cancer center will facilitate interactions with the many stakeholders in the cancer research and care ecosystem.


“He also has strong interpersonal and communication skills that will serve the community well, particularly with Congress and its support for the NIH,” DePinho said. “A good day for cancer patients, bad day for cancer.”


UNC officials said Sharpless would not be granting interviews until he is officially named NCI director.


Sharpless’s research is focused on the control of the cell cycle, particularly by the INK4a/ARF (or CDKN2a) tumor suppressor locus which encodes the p16INK4a and ARF cancer suppressors.


“It’s a challenging thing for a new director to come in from the outside and gain the trust and sympathy of the programs that have their own culture and history,” said Keith Flaherty, professor of medicine at Harvard Medical School, director of Henri and Belinda Termeer Center for Targeted Therapy, Cancer Center, Massachusetts General Hospital, and director of Clinical Research, Cancer Center, Massachusetts General Hospital.


“I think Ned is the perfect candidate to quickly gain people’s trust in that environment. He is absolutely perfectly suited to reach out to the extramural program, which is critical at this time,” Flaherty added.


“I think it’s not an easy environment to walk into financially,” he said.


The president’s budget proposal seeks to slash NIH by 21 percent and cut indirect costs charged by institutions that house NIH-funded researchers (The Cancer Letter, May 26).


Flaherty said Sharpless would be an excellent advocate for NCI on Capitol Hill and within the administration.


“It’s all right up his alley,” said Flaherty, who has worked with Sharpless throughout his career. “Ned is all about pressing on the accelerator in the areas where resources would yield more discoveries. So, I think it’s a great time for him to be getting a chance to weigh in on that.”


After nine years at Harvard institutions, Sharpless returned to UNC in 2002 as an assistant professor of medicine and genetics. He has been director of the UNC cancer center since Jan. 1, 2014. He was an internal candidate, who succeeded his mentor H. Shelton “Shelley” Earp.


With Sharpless’s departure for Bethesda, Earp, professor of pharmacology and medicine and a Lineberger Professor of Cancer Research, will step in as interim director.


“Ned Sharpless is an exceptional choice as the next NCI director,” Earp said to The Cancer Letter. “He will be sorely missed at the home institution, where he was educated and then developed his faculty career, but we are proud to contribute to the nation’s cancer leadership.


“When Ned was appointed the third UNC Lineberger director, I told The Cancer Letter that he had an encyclopedic knowledge of cancer biology and a chief resident’s grasp of medicine and oncology,” Earp said. “These attributes have not faded. What he has done is to add substantial strategic and administrative experience.


“His leadership of a center with a nation-leading population science effort has produced a deep appreciation of the field from community prevention to big data assessment of cancer outcomes,” Earp said. “All the while, his lab program continued to thrive, not surprising for one as dedicated as Ned to understanding the disease at its molecular level.


“What is perhaps more impressive is that he kept attending on the leukemia service and participating in the scholarly training of medical oncologists,” Earp said. “These roles kept him close to the lives of patients and families confronted with a cancer diagnosis and its personal and financial impact. Ned will be a superb and impartial steward of the crucial resources allocated to the NCI.


“Come March, however, we will know where his allegiance will lie,” said Earp, referring to March Madness, the NCAA Division I Men’s Basketball Tournament, which provides true North Carolinians—Sharpless hails from Greensboro—with an excuse to go batshit.


Richard Goldberg, director of West Virginia University Cancer Institute and former physician-in-chief of the North Carolina Cancer Hospital, said Sharpless has the capacity to provide clear vision to NCI.


“I couldn’t be happier,” Goldberg said to The Cancer Letter. “He is very well liked, because he is a good human being who follows logical principles. He has his finger on the pulse of everything that is important to a cancer center director. He is clinical. He understands patient-related problems, he has a lab, he is R01-funded, he has run a cancer center, so he knows how NCI facilitates and holds back the cancer centers at the same time. He will recognize the need for basic science discovery to apply to the clinical needs of cancer patients in a way that only someone with the lab and clinical practice experience can do.


“He will be an articulate spokesman to represent the value of cancer research and all of its elements to the executive branch of government.”


Goldberg described UNC Lineberger as “a flagship cancer program in the country.”


“It really does interesting basic science, population science and clinical work,” Goldberg said. “The fact that UNC has such strong school of public health, school of pharmacy and school of medicine means that Ned understands how to integrate all of these disciplines in a meaningful way.”


Sharpless isn’t an expert in population sciences, but as center director at UNC he immediately grasped the importance of this area of research, said Ethan Basch, director of the Cancer Outcomes Research Program, professor at the UNC-Chapel Hill Department of Medicine in the Division of Hematology and Oncology, and a member of the NCI Board of Scientific Advisors.


“When Ned became the cancer center director, he immediately recognized that population science is a strength at UNC, and he worked very hard to educate himself and to immerse himself into health services and population science,” Basch said.


“He met very regularly with the population science leadership—that would be Andy Olshan [associate director, population sciences at the cancer center], Kurt Ribisl [professor at the Department of Health Behavior and program leader, cancer prevention and control at the cancer center], Melissa Troester [research associate professor at the Department of Pathology and Laboratory Medicine], and myself—and we had monthly meetings with him, and he put tremendous support into the population science initiatives.


“He started an initiative in the state to try to narrow disparities by providing screening services in these hot spots where we found through our surveillance programs that people do not get their colon cancer screening and there is an excess of deaths related to colon cancer,” Basch said. “He put substantial cancer center resources into that. He is not a population scientist, and he acknowledges that, but I think as a result of that he puts in an extra effort to try to focus in that area.”


Sharpless’s appointment represents a generational change in cancer research, said Neil Hayes, an associate professor at the UNC Division of Hematology/Oncology, Department of Otolaryngology/Head and Neck Cancer Surgery, and a colleague at UNC who has worked with Sharpless closely over the past 13 years.


“He is from a generation of trainees from Dana-Farber,” Neil Hayes said. “He is of the generation of like-minded people who grew up in the genomic age around the turn of the 21st century, with the first generation of genomics assays, and that style of thinking. Although Ned himself was trained more classically by Ron DePinho, he is sort of a self-made man, but trained by great mentors.


“He is broad in his exposure to cancer research, certainly on the basic science side. He has been working on the health services side. He has treated his colleagues and his students fairly and kindly,” DePinho said.


Sharpless is also involved in developing oncology applications for IBM Watson. Recently, he described that artificial intelligence program on the CBS News program 60 Minutes.


Colleagues Hayes and Basch also expect that Sharpless will take a calm, rational approach to running NCI.


“His style is very collaborative. He is a listener,” said Hayes. “I think he is someone who can work well with Francis Collins, who has a UNC connection. Francis certainly comes through UNC fairly often. I think the Collins initiatives including the Cancer Genome Atlas have been at the core of what UNC has worked on for the past ten years or so, so Ned would be sympathetic to that kind of thinking.”


Basch predicts that Sharpless will be systematic in his approach to learning the ropes at NCI.


“He will meet with the leadership at NCI to look at the portfolio,” Basch said. “He is very interested in making sure the dollars are being spent meaningfully and efficiently. I think he will probably spend some time trying to get his head around where the support is going and making sure that he feels comfortable that meaningful outcomes are going to be produced.


“That shouldn’t be a problem, because at this moment NCI is pretty well organized in that way. I am quite impressed on the BSA with the thoughtfulness of the direction of the funding. I think he is also going to think about strategic directions moving forward. Ned is really a forward-looking guy. I think one of the questions would be around some of the moonshot allocations, because a lot of that is already in motion.,” Basch said.


“At the upcoming BSA this week we will be reviewing many of the concepts that came out of that initiative. I think it’s a great opportunity for Ned and a great opportunity for NCI to take a look at those RFAs that are being developed and to make sure that they are aligned with the state of the science,” Basch said.


Sharpless is likely to take a relatively small salary cut when he comes to NCI. According to state figures, his pay package now is just $402,870. NIH institute directors, if they are hired under the Title 42 program, can earn up to $335,000.

He will likely have to divest from the companies he founded, observers say. One of these companies, G1 Therapeutics Inc., recently went public. The other, HealthSpan Diagnostics, is at an earlier stage.


“I don’t know any details of this, but am confident, knowing Ned, that he is approaching this with integrity and thoughtfulness,” Basch said.


NIH Director Collins, who has strong support on Capitol Hill, may be in a position to protect NIH at a time when the administration appears to value biomedical research less than it values defense and border security.


Collins, who is 67, graduated from the UNC School of Medicine and did his internship and residency at North Carolina Memorial Hospital in Chapel Hill.


“[Sharpless] has travelled a scientific path of considerable distinction,” Collins said in a statement. “A practicing oncologist caring for patients with leukemia, Dr. Sharpless also leads a highly productive research group studying the cell cycle and its role in cancer and aging. He has authored more than 150 original scientific papers, reviews and book chapters, and holds 10 patents.


“Dr. Sharpless is an elected member of the American Society of Clinical Investigation and the Association of American Physicians,” Collins said. “He also serves on the Association of American Cancer Institutes’ board of directors, and on the NIH’s National Institute of Aging’s National Advisory Council on Aging. He is a co-founder of G1 Therapeutics, a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapeutics for the treatment of cancer.


“I’ve known Dr. Sharpless professionally for many years as an outstanding scientist, clinician, and administrator, and we are very fortunate to have him join the NIH leadership team.”


Sharpless’s appointment was announced late Friday, well after the president left Washington, as part of a large number of appointments. NCI officials appear not to have been given a heads-up about the upcoming appointment. However, in a statement, Collins thanked Lowy for his service.


“I want to take this opportunity to express my profound gratitude to Doug Lowy, who has served brilliantly as the Acting NCI director, since Dr. Harold Varmus’ departure in the spring of 2015,” Collins said. “Dr. Lowy skillfully took the reins at NCI and led the agency as it developed and implemented the NIH component of the Beau Biden Cancer Moonshot Initiative, as well as many other important programs and scientific ventures.


“But if you knew Dr. Lowy only by his modest manner, you would miss the fact that he’s a world-class, award-winning scientist who has changed the face of public health with his research advances. We are deeply indebted to Dr. Lowy for his leadership and his commitment to improving people’s health, curing disease, and saving lives.”


In an email to NCI staff, Lowy said his goal for the past two years has been “to provide the institute and the entire cancer community with leadership, scientific vision, and consistency, so that we make even greater progress on behalf of cancer patients.


“You have my everlasting gratitude for the confidence and strong support you have given me,” Lowy wrote to the staff. “Our many accomplishments would not have been possible without the passion, dedication, and intelligence you bring to your work every day.”


“Dr. Sharpless is a leader and visionary in the field, and heads one of the nation’s premier academic medical centers,” said Friends of Cancer Research Chairperson & Founder, Ellen Sigal. “With his leadership, I have no doubt that NCI will continue in a manner best benefitting patients since Dr. Sharpless understands not only how to manage and mentor young scientists, but the importance of sustained research funding to continue cultivating revolutionary ideas and treatments. I would also like to thank Dr. Lowy for his incredible service as NCI acting director, and look forward to continuing to work with him as one of the country’s top cancer scientists.”


Like Collins, an Obama appointee, Sharpless could not have been chosen based on his politics.


Federal Election Commission records show that he has made campaign contributions to Democrats, including a $250 contribution to the Obama-Biden ticket in 2008 and a $500 contribution to the Obama Victory Fund in 2012.