Tag: Profiles

Meet Shanta Dhar

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Shanta Dhar
Shanta Dhar
Fields: Chemistry and cancer immunotherapy
Works at: University of Georgia, Athens
Born and raised in: Northern India
Studied at: Indian Institute of Science, Bangalore; Johns Hopkins University, Baltimore, Md.; and Massachusetts Institute of Technology, Cambridge, Mass.
To unwind: She hits the gym
Credit: Frankie Wylie, Stylized Portraiture

The human body is, at its most basic level, a giant collection of chemicals. Finding ways to direct the actions of those chemicals can lead to new treatments for human diseases.

Shanta Dhar, an assistant professor of chemistry at the University of Georgia, Athens (UGA), saw this potential when she was exposed to the field of cancer immunotherapy as a postdoctoral researcher at the Massachusetts Institute of Technology. (Broadly, cancer immunotherapy aims to direct the body’s natural immune response to kill cancer cells.) Dhar was fascinated by the idea and has pursued research in this area ever since. “I always wanted to use my chemistry for something that could be useful [in the clinic] down the line,” she said.

A major challenge in the field has been training the body’s immune system—specifically the T cells—to recognize and attack cancer cells. The process of training T cells to go after cancer is rather like training a rescue dog to find a lost person: First, you present the scent, then you command pursuit.

The type of immune cell chiefly responsible for training T cells to search for and destroy cancer is a called a dendritic cell. First, dendritic cells present T cells with the “scent” of cancer (proteins from a cancer cell). Then they activate the T cells using signaling molecules.

Dhar’s Findings

Dhar’s work focuses on creating the perfect trigger for cancer immunotherapy—one that would provide both the scent of cancer for T cells to recognize and a burst of immune signaling to activate the cells.

Using cells grown in the lab, Dhar’s team recently showed that they could kill most breast cancer cells using a new nanotechnology technique, then train T cells to eradicate the remaining cancer cells.

For the initial attack, the researchers used light-activated nanoparticles that target mitochondria in cancer cells. Mitochondria are the organelles that provide cellular energy. Their destruction sets off a signaling cascade that triggers dendritic cells to produce one of the proteins needed to activate T cells.

Because the strategy worked in laboratory cells, Dhar and her colleague Donald Harn of the UGA infectious diseases department are now testing it in a mouse model of breast cancer to see if it is similarly effective in a living organism.

For some reason, the approach works against breast cancer cells but not against cervical cancer cells. So the team is examining the nanoparticle technique to see if they can make it broadly applicable against other cancer types.

Someday, Dhar hopes to translate this work into a personalized cancer vaccine. To create such a vaccine, scientists would remove cancer cells from a patient’s body during surgery. Next, in a laboratory dish, they would train immune cells from the patient to kill the cancer cells, then inject the trained immune cells back into the patient’s body. If the strategy worked, the trained cells would alert and activate T cells to eliminate the cancer.

Meet Emily Scott

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Emily Scott
Emily Scott
Field: Biochemistry
Works at: University of Kansas in Lawrence
Favorite hobby: Scuba diving
Likes watching: “Law & Order”
Likes reading: True-life survival stories
Credit: Chuck France, University of Kansas

With an air tank strapped to her back, college student Emily Scott dove to the bottom of the Gulf of Mexico to examine life in an oxygen-starved area called the Dead Zone. The bottom waters had once teemed with red snapper, croaker and shrimp, but to Scott, the region appeared virtually devoid of life. Then, from out of the mud, appeared the long, undulating arms of a brittle star.

As Scott learned, that particular species of brittle star survived in the Dead Zone because it has something many other marine creatures don’t: an oxygen-carrying protein called hemoglobin. This same protein makes our blood red. Key to hemoglobin’s special oxygen-related properties is a small molecular disk called a heme (pronounced HEEM).

Once she saw what it meant to brittle stars, Scott was hooked on heme and proteins that contain it.

Scott’s Findings

Now an associate professor, Scott studies a family of heme proteins called cytochromes P450 (CYP450s). These proteins are enzymes that facilitate many important reactions: They break down cholesterol, help process vitamins and play an important role in flushing foreign chemicals out of our systems.

To better understand CYP450s, Scott uses a combination of two techniques–X-ray crystallography and nuclear magnetic resonance spectroscopy—for capturing the enzymes’ structural and reactive properties.

She hopes to apply her work to design drugs that block certain CYP450 reactions linked with cancer. One target reaction, carried out by CYP2A13, converts a substance in tobacco into two cancer-causing molecules. Another target reaction is carried out by CYP17A1, an enzyme that helps the body produce steroid sex hormones but that, later in life, can fuel the uncontrolled growth of prostate or breast cancer cells.

“I’m fascinated by these proteins and figuring out how they work,” Scott says. “It’s like trying to put together a puzzle—a very addictive puzzle.” Her drive to uncover the unknown and her willingness to apply new techniques have inspired the students in her lab to do the same.

Content adapted from “Hooked on Heme,” an article in the September 2013 issue of Findings magazine.

Meet Brad Duerstock

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Brad Duerstock
Brad Duerstock
Fields: Neuroscience, assistive technology design
Works at: Purdue University, West Lafayette, IN
Hobbies: Gadgetry, architectural design
Bizarre collectible: Ecuadorian shrunken head (not a real one—it’s a replica made from goatskin)
Credit: Andrew Hancock, Purdue University

At the age of 18, Brad Duerstock had a devastating accident. A star member of his high school swim team, Duerstock hit his head during practice in a way that broke his neck and paralyzed all of his limbs. Today, he studies spinal cord injuries much like his own, investigating how the damage occurs and how it could possibly be repaired.

Duerstock has worked to make science accessible to people with disabilities, whether they use wheelchairs, as he does, or have visual or other impairments. For example, he has redesigned laboratory space to make it easier for people with disabilities to navigate and perform tasks.

“I like knowing that what I do can ultimately impact others,” Duerstock says.

Duerstock’s Findings

Much of Duerstock’s research deals with what occurs immediately following a nerve injury. In a spinal cord injury, nerve tissue becomes severed or dies. The immune response and bleeding in the injured area can cause extra damage to nerves in the spinal cord. Duerstock and his team have found that a molecule called acrolein is produced in spinal cord injuries and that it kills the nerves it encounters as it spreads around the injury site. They have been investigating a compound called polyethylene glycol (PEG), a polymer that could seal ruptured nerve cell membranes, possibly protecting nerve tissue from further damage immediately following a spinal cord injury.

Duerstock also founded and leads the Institute for Accessible Science (IAS), a community of scientists, students, parents and teachers whose goal is to promote better accommodations for people with disabilities who are studying or working in the sciences. The IAS looks into how to redesign lab spaces and equipment to increase accessibility for people with disabilities, particularly those with limited mobility or vision.

Although Duerstock originally wanted to be a doctor, he believes his true calling is in research. “The sense of discovery and the impact on others are big motivations for me,” says Duerstock. “Being a researcher, you might have a broader impact on society than you would as a practicing physician.”

Content adapted from the NIGMS Findings magazine article Opening Up the Lab.

Chemist Phil Baran Joins “Genius” Ranks as MacArthur Fellow

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Cake decorated with a two-dimensional structure of the molecule, stephacidin B
When Baran’s research team succeeds in synthesizing an important natural product, the group sometimes celebrates with a cake decorated with a two-dimensional structure of the molecule. This molecule, stephacidin B, was isolated from a fungus and has anticancer properties. See images of other Baran lab cakes.

As a newly appointed MacArthur Fellow, Phil Baran is now officially a genius. The MacArthur award recognizes “exceptionally creative” individuals who have made significant contributions to their field and are expected to continue doing so. Baran, a synthetic organic chemist at Scripps Research Institute in La Jolla, Calif., was recognized today for “inventing efficient, scalable, and environmentally sound methods” for building, from scratch, molecules produced in nature. Many of these natural products have medicinal properties. Baran has already concocted a host of natural products, including those with the ability to kill bacteria or cancer cells. In addition to emphasizing the important pharmaceutical applications of his work, Baran embraces its creative aspects: “The area of organic chemistry is such a beautiful one because one can be both an artist and an explorer at the same time,” he said in the MacArthur video interview Exit icon.

Learn more:

NIGMS “Meet a Chemist” Profile of Baran
NIH Director’s Blog Post on Baran’s Recent Work

Meet Galina Lepesheva

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Galina Lepesheva
Galina Lepesheva
Field: Biochemistry
Works at: Vanderbilt University, Nashville, TN
Born, raised and studied in: Belarus
To unwind, she: Reads, travels, spends time with her family

Galina Lepesheva knows that kissing bugs are anything but romantic. When the lights get low, these blood-sucking insects begin feasting—and defecating—on the faces of their sleeping victims. Their feces are often infected with a protozoan (a single-celled, eukaryotic parasite) called Trypanosoma cruzi that causes Chagas disease. Lepesheva has developed a compound that might be an effective treatment for Chagas. She has also tested the substance, called VNI, as a treatment for two related diseases—African sleeping sickness and leishmaniasis.

“This particular research is mainly driven by one notion: Why should people suffer from these terrible illnesses if there could be a relatively easy solution?” she says.

Lepesheva’s Findings

Currently, most cases of Chagas disease occur in rural parts of Mexico, Central America and South America. According to some estimates, up to 1 million people in the U.S. could have Chagas disease, and most of them don’t realize it. If left untreated, the infection is lifelong and can be deadly.

The initial, acute stage of the disease is usually mild and lasts 4 to 8 weeks. Then the disease goes dormant for a decade or two. In about one in three people, Chagas re-emerges in its life-threatening, chronic stage, which can affect the heart, digestive system or both. Once chronic Chagas disease develops, about 60 percent of people die from it within 2 years.

The Centers for Disease Control and Prevention (CDC) has targeted Chagas disease as one of five “neglected parasitic infections,” indicating that it warrants special public health action.

“Chagas disease does not attract much attention from pharmaceutical companies,” Lepesheva says. Right now, there are only two medicines to treat it. They are only available by special request from the CDC, aren’t always effective and can cause severe side effects.

Lepesheva’s research focuses on a particular enzyme, CYP51, that is the target of some anti-fungal medicines. If CYP51 can also act as an effective drug target for the parasites that cause Chagas, her work might help meet an important public health need.

CYP51 is found in all kingdoms of life. It helps produce molecules called sterols, which are essential for the development and viability of eukaryotic cells. Lepesheva and her colleagues are studying VNI and related compounds to examine whether they can block the activity of CYP51 in human pathogens such as protozoa, but do no harm to the enzyme in mammals. In other words, her goal is to cripple disease-causing organisms without creating side effects in infected humans or other mammals.

Lepesheva has tested the effectiveness of VNI on Chagas-infected mice. Remarkably, it has worked 100 percent of the time, curing both the acute and chronic stages of the disease. It acts by preventing the protozoan from establishing itself in the host’s body. If it is similarly effective in humans, VNI could become the first reliable treatment for Chagas disease.

Meet David Patterson

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David Patterson
David Patterson
Field: Psychology
Works at: University of Washington, Seattle
Alternative career: Full-time rock ‘n’ roll drummer
Hobbies: Part-time rock ‘n’ roll drummer (with his band, the Shrinking Heads)
Credit: Clare McLean, UW Medicine Strategic Marketing & Communications

The pain stemming from second- and third-degree burns is among the worst known. Throughout recovery, the intense, disabling pain patients feel can lead to sleeplessness, anxiety and depression.

David Patterson first entered a burn ward as a psychologist hoping to help patients cope with these issues. He saw patients refuse wound cleaning because of how painful it could be.

“I’ve learned how horribly difficult it is to control burn and trauma pain with medications alone,” he says. “The amount of pain people feel affects how well they adjust in the long term.” Pain and the mental, social and emotional problems it causes also hinder the body’s ability to heal physically.

Today, Patterson is committed to helping burn patients overcome pain, allowing their bodies—as well as their minds—to heal more efficiently. Using virtual reality (VR) technology, Patterson has found an effective complement to pain-relieving drugs such as morphine and other opioid analgesics.

Patterson’s Findings

“To be honest, for acute pain, you give someone a shot or a pill and it’s instant relief,” Patterson says. But opioid analgesics carry problems.  Sometimes patients don’t respond well to morphine or require high dosages that carry strong side effects.

When burn patients undergo routine wound care, the pain can be excruciating—as bad as or worse than the original burn incident. Realizing the brain can take only so many stimuli, Patterson collaborated with fellow UW psychologist Hunter Hoffman to experiment with VR in pain relief. When combined with minimal pain medications, VR is a powerful solution to acute pain. By providing a computer-generated reality—for example, an icy canyon filled with snowmen and Paul Simon’s music, as in the case of their creation SnowWorld—the patient’s eyes, ears and mind are so occupied that he or she can effectively ignore the pain.

Patterson and his team found that VR pain reduction strategies are as powerful as opioid analgesics, without the negative side effects. The technology doesn’t require specialized expertise and is getting progressively less expensive, making it economically attractive.  At least eight hospitals have adopted the methods as part of their clinical program, allowing Patterson an opportunity to conduct further studies on the long-term effects of using these complementary methods and the efficacy of the techniques on other kinds of pain.

Learn more:
SnowWorld News Segment Featured on NBC’s Rock Center Exit icon