Tag: Precision Medicine

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Three Brothers Are Making Research a Family Affair

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From left to right: Caleb, Paul, and Adam Worsley sitting on stools in a chemistry lab.
Caleb, Paul, and Adam Worsley. Credit: Pittsburg State University.

“You’re doing something really important with people who are important to you,” Paul Worsley remarks when asked about having his younger brothers Caleb and Adam as lab mates. The trio are undergraduate students working in the lab of Santimukul Santra, Ph.D., at Pittsburg State University in Pittsburg, Kansas.

Paul seated at his chemistry fume hood. Credit: Pittsburg State University.

All three brothers are part of the Kansas IDeA Networks of Biomedical Research Excellence (K-INBRE). Paul is currently a junior majoring in biology and history. He plans to go to medical school when he graduates, but his time in the lab has given him a love for research—and has even led him to toy with the idea of going to graduate school instead. His twin brothers Caleb and Adam are only freshmen, but they both think they want to pursue scientific research when they graduate.

When Paul was a sophomore, he applied for a K-INBRE research spot in Dr. Santra’s lab and was immediately accepted. He quickly realized that organic chemistry in the lab was much different—and more exciting—than anything he’d seen in the classroom. “I like organic synthesis because it really tests your knowledge,” he says. “Answering exam questions is way different than actually doing it in a lab.” Despite the challenges that came with research, Paul was clearly doing great work because one day Dr. Santra joked, “Hey, you got any brothers?” Paul responded, “Actually, yes.”

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Block an Enzyme, Save a Life

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Vern Schramm in his lab, dressed in a white lab coat, standing with his arms folded across his chest. Vern Schramm, professor of biochemistry at Albert Einstein College of Medicine, Bronx, New York. Credit: Albert Einstein College of Medicine.

Enzymes drive life. Without them, we couldn’t properly digest food, make brain chemicals, move—or complete myriad other vital tasks. Unfortunately, in certain cases, enzymes also can trigger a host of health problems, including cancer, bacterial infections, and hypertension (high blood pressure).

Understanding how enzymes work has been the research focus of Vern Schramm for more than 4 decades.

“When we started our work, we were driven not by the desire to find drugs, but to understand the nature of enzymes, which are critical to human life,” Schramm says. But his research already led to one drug, and promises many more.

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PECASE Honoree Elizabeth Nance Highlights the Importance of Collaboration in Nanotechnology

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Black and white microscopic image of a capillary supplying blood to brain cells. A network of capillaries supplies brain cells with nutrients. Tight seals in their walls keep blood toxins—and many beneficial drugs—out of the brain. Credit: Dan Ferber, PLOS Biol 2007 Jun; (5)6:E169. CC by 2.5 Link to external web site.

The blood-brain barrier—the ultra-tight seal in the walls of the brain’s capillaries—is an important part of the body’s defense system. It keeps invaders and other toxins from entering the human brain by screening out dangerous molecules. But the intricate workings of this extremely effective barrier also make it challenging to design therapeutics that would help us. And as it turns out, getting a drug across the blood-brain barrier is only half the battle. Once it’s across, the drug needs to effectively target the right cells in the brain tissue. With this in mind, it’s no surprise that challenges this complex are solved through collaboration among scientists from several different specialties.

Elizabeth Nance Link to external web site, an assistant professor of chemical engineering at the University of Washington in Seattle and a recent recipient of the Presidential Early Career Award for Scientists and Engineers (PECASE), focuses her research on understanding the barriers in the brain and other cell- and tissue-based barriers in the body to see how nanoparticles interact with them. Her lab uses nanoparticles to package therapies that will treat newborn brain injury, which can occur when the brain loses oxygen and blood flow, often during or immediately prior to delivery. This damage can lead to cerebral palsy, developmental delays, or sometimes death. Early interventions for newborn brain injury can be valuable, but they need to target specific, injured cells without harming healthy ones.

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Interview With a Scientist: Namandjé Bumpus, Drug Metabolism Maven

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Medications are designed to treat diseases and make us healthier. But our bodies don’t know that. To them, medications are merely foreign molecules that need to be removed.

Before our bodies can get rid of these drug molecules, enzymes in the liver do the chemical work of preparing the molecules for removal. There are hundreds of different versions of these drug-processing enzymes. Some versions work quickly, others work slowly. In some cases, the versions you have determine how well a medication works for you, and whether you experience side effects from it.

Namandjé Bumpus, a researcher at Johns Hopkins University School of Medicine, is interested in how human bodies respond to HIV medications. She studies the enzymes that process these drugs. Her research team discovered that a genetic variant of a liver enzyme impacts the way some people handle a particular HIV drug. This variant is found in around 80 percent of people of European descent. She describes her work in this video.

Bumpus recently presented her research to a more scientifically advanced audience at an Early Career Investigator Lecture at the National Institutes of Health. Watch her talk titled Drug Metabolism, Pharmacogenetics and the Quest to Personalize HIV Treatment and Prevention.

Dr. Bumpus’ work is supported in part by NIGMS grant R01GM103853.

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New Streamlined Technique for Processing Biological Samples

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Illustration of Slug flow microextraction.
Researchers have discovered a faster, easier and more affordable technique for processing biological samples. Credit: Weldon School of Biomedical Engineering, Purdue University.

It’s not unusual for the standard dose of a drug to work well for one person but be less effective for another. One reason for such differences is that individuals can break down drugs at different rates, leading to different concentrations of drugs and of their breakdown products (metabolites) in the bloodstream. A promising new process called slug-flow microextraction could make it faster, easier and more affordable to regularly monitor drug metabolites so that medication dosages could be tailored to each patient’s needs, an approach known as personalized medicine. This technique could also allow researchers to better monitor people’s responses to new drug treatments during clinical trials. Continue reading “New Streamlined Technique for Processing Biological Samples”

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Understanding Complex Diseases Through Computation

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Scientists developed a computational method that could help identify various subtypes of complex diseases. Credit: Stock image

Complex diseases such as diabetes, cancer and asthma are caused by the intricate interplay of genetic, environmental and lifestyle factors that vary among affected individuals. As a result, the same medications may not work for every patient. Now, scientists have shown that a computational method capable of analyzing more than 100 clinical variables for a large group of people can identify various subtypes of asthma, which could ultimately lead to more targeted and personalized treatments. The research team, led by Wei Wu Exit icon of Carnegie Mellon University and Sally Wenzel of the University of Pittsburgh, used a computational approach developed by Wu to identify several patient clusters consistent with known subtypes of asthma, as well as a possible new subtype of severe asthma that does not respond well to conventional drug treatment. If supported by further studies, the researchers’ proposed approach could help improve the understanding, diagnosis and treatment not just of asthma but of other complex diseases.

This work also was funded by NIH’s National Heart, Lung, and Blood Institute.

Learn more:
Carnegie Mellon University News Release Exit icon

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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.

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Genetic Discovery Could Enable More Precise Prescriptions

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Prescription pad with DNA illustration on it. Credit: Jane Ades, NIH’s National Human Genome Research Institute.
New insight into the genes that affect drug responses may help doctors prescribe the medications and doses best suited for each individual. Credit: Jane Ades, NIH’s National Human Genome Research Institute.

Scientists know that variations in certain genes can affect the way a person responds to medications. New research by Wolfgang Sadee Exit icon at Ohio State University shows that drug responses also depend on previously overlooked parts of DNA—sections that regulate genes, but are not considered genes themselves. This study focused on an important enzyme abbreviated CYP2D6 that processes about one-fourth of all prescription drugs. Differences in the enzyme’s performance, which range from zilch to ultra-rapid, can dramatically alter the effectiveness and safety of certain medications. Researchers discovered two new genetic variants that impact CYP2D6 performance. One of these, located in a non-gene, regulatory region of DNA, doubles or even quadruples enzyme activity. Coupling these findings with genetic tests could help doctors better identify each patient’s CYP2D6 activity level, enabling more precise prescriptions. The findings also open up a whole new area of investigation into genetic factors that impact drug response.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Learn more:

Ohio State University News Release (no longer available)

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New Approach Subtypes Cancers by Shared Genetic Effects

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Cancer

Cancer tumors are like snowflakes—no two ever share the same genetic mutations. Their unique characteristics make them difficult to categorize and treat. A new approach proposed by Trey Ideker and his team at the University of California, San Diego, might offer a solution. Their approach, called network-based stratification (NBS), identifies cancer subtypes by how different mutations in different cancer patients affect the same biological networks, such as genetic pathways. As proof of principle, they applied the method to ovarian, uterine and lung cancer data to obtain biological and clinical information about mutation profiles. Such cancer subtyping shows promise in helping to develop more effective, personalized treatments.

Learn more:

University of California, San Diego News Release
Ideker Lab