Creative Minds: Using Machine Learning to Understand Genome Function

Anshul Kundaje

Anshul Kundaje / Credit: Nalini Kartha

Science has always fascinated Anshul Kundaje, whether it was biology, physics, or chemistry. When he left his home country of India to pursue graduate studies in electrical engineering at Columbia University, New York, his plan was to focus on telecommunications and computer networks. But a course in computational genomics during his first semester showed him he could follow his interest in computing without giving up his love for biology.

Now an assistant professor of genetics and computer science at Stanford University, Palo Alto, CA, Kundaje has received a 2016 NIH Director’s New Innovator Award to explore not just how the human genome sequence encodes function, but also why it functions in the way that it does. Kundaje even envisions a time when it might be possible to use sophisticated computational approaches to predict the genomic basis of many human diseases.

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FDA Approves First CAR-T Cell Therapy for Pediatric Acute Lymphoblastic Leukemia

Emily Whitehead

Caption: Cancer survivor Emily Whitehead with her dog Lucy.
Credit: Emily Whitehead Foundation

Tremendous progress continues to be made against the Emperor of All Maladies, cancer. One of the most exciting areas of progress involves immunotherapy, a treatment strategy that harnesses the natural ability of the body’s own immune cells to attack and kill tumor cells. A lot of extremely hard work has gone into this research, so I was thrilled to learn that the Food and Drug Administration (FDA) just announced today its first approval of a promising type of immunotherapy called CAR-T cell therapy for kids and young adults with B-cell acute lymphoblastic leukemia (ALL)—the most common childhood cancer in the U.S.

ALL is a cancer of white blood cells called lymphocytes. Its treatment with chemotherapy drugs, developed with NIH support, has transformed ALL’s prognosis in kids from often fatal to largely treatable: about 90 percent of young patients now recover. But for those for whom the treatment fails, the prognosis is grim.

In the spring of 2012, Emily Whitehead of Philipsburg, PA was one such patient. The little girl was deathly ill, and her parents were worried they’d run out of options. That’s when doctors at Children’s Hospital of Philadelphia gave Emily and her parents new hope. Carl June and his team had successfully treated three adults with their version of CAR-T cell therapy, which is grounded in initial basic research supported by NIH [1,2]. Moving forward with additional clinical tests, they treated Emily—their first pediatric patient—that April. For a while, it was touch and go, and Emily almost died. But by May 2012, her cancer was in remission. Today, five years later, 12-year-old Emily remains cancer free and is thriving. And I’ve had the great privilege of getting to know Emily and her parents over the last few years.

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You’ll Want to See This! “First in Human” Debuts August 10

For over 60 years, the NIH Clinical Center—the world’s largest hospital dedicated to clinical research—has been at the forefront of developing treatments for our most deadly and damaging diseases. It’s here at our “House of Hope” in Bethesda, MD, where, among many other medical firsts, chemotherapy was first used to treat cancerous tumors, gene therapy underwent its first human tests, surgeons first successfully replaced the heart’s mitral valve, and the first anti-viral drug for HIV/AIDS met with early success.

Now, in a Discovery Channel documentary called First in Human, millions of people all around the globe will get a chance to see the doctors, nurses, and other staff of NIH’s remarkable research hospital in action. Narrated by Big Bang Theory star Jim Parsons, the three-part series debuts at 9 p.m.-11 p.m., ET, Thursday, August 10. The second and third segments will air at the same time on August 17 and 24. For a sneak peak, check out the video clip above!

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Tumor Scanner Promises Fast 3D Imaging of Biopsies

UW light sheet microscope team

Caption: University of Washington team that developed new light-sheet microscope (center) includes (l-r) Jonathan Liu, Adam Glaser, Larry True, Nicholas Reder, and Ye Chen.
Credit: Mark Stone/University of Washington

After surgically removing a tumor from a cancer patient, doctors like to send off some of the tissue for evaluation by a pathologist to get a better idea of whether the margins are cancer free and to guide further treatment decisions. But for technical reasons, completing the pathology report can take days, much to the frustration of patients and their families. Sometimes the results even require an additional surgical procedure.

Now, NIH-funded researchers have developed a groundbreaking new microscope to help perform the pathology in minutes, not days. How’s that possible? The device works like a scanner for tissues, using a thin sheet of light to capture a series of thin cross sections within a tumor specimen without having to section it with a knife, as is done with conventional pathology. The rapidly acquired 2D “optical sections” are processed by a computer that assembles them into a high-resolution 3D image for immediate analysis.

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Precision Oncology: Gene Changes Predict Immunotherapy Response

Cancer Immunotherapy

Caption: Adapted from scanning electron micrograph of cytotoxic T cells (red) attacking a cancer cell (white).
Credits: Rita Elena Serda, Baylor College of Medicine; Jill George, NIH

There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.

A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.

Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy [1]. After a year of biweekly infusions, more than half of the patients had their tumors shrink by at least 30 percent—and, even better, 18 had their tumors completely disappear!

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