Category: All Spotlights

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The Heart of Research

As we uncover previously unknown truths about the world surrounding us, scientific research becomes more complex making interdisciplinary research vital to the progress of human health.

Dr. Michael Greenberg is an Assistant Professor of Biochemistry and Molecular Biophysics who has made the very core of his lab interdisciplinary in nature. Greenberg’s lab is at the epicenter of biochemistry, biophysics, and cellular biology. His lab studies cytoskeletal motors using physics to explain cellular movements.

His interest in the intersection of these fields started as early as his undergraduate experience at Brandeis University where he triple-majored in physics, chemistry, and biological physics.

“Initially I thought I was going to study string theory,” Greenberg said. “I realized pretty quickly that I didn’t want to sit with a pencil and paper all day. For me, it was more fun to learn about string theory than it was to do it on your own.”

From there, Greenberg spent his graduate career and postdoctoral fellowship studying molecular motor mechanics with Dr. Jeffrey Moore and Dr. Michael Ostap, respectively. These experiences collectively inspired him to begin his own lab studying how cytoskeletal motors function in health and disease. His goal is to explain the way cells and molecules move using physics and modeling. However, before starting his own lab, Greenberg had little experience with cell culture.

“There are lots of really interesting questions in biology for people with physics backgrounds to tackle,” Greenberg said. “We use physics-based models and techniques to try to understand biological systems.”

In his pursuit to understand how cells and tissues move at a molecular level, Greenberg’s lab has become adept in utilizing human engineered heart tissues. These model tissues are three-dimensional, and have the ability to contract similar to a human heart. Greenberg’s lab builds the human engineered heart tissues from scratch using Matrigel, collagen, stem cell-derived cardiomyocytes, and stem cell-derived fibroblasts.

“The tissues will self-assemble between two sticks and they will contract,” Greenberg said. “We can take two electrodes, put them on the sides of the tissue, and hook them up to a signal generator. We can also take these tissues and apply mechanical loads to see how that affects contractility.”

When reports of SARS-CoV-2 patients dying of heart failure reached the department, Greenberg, Dr. Kory Lavine (Department of Medicine; Division of Cardiology), and Dr. Michael Diamond (Department of Medicine; Division of Infectious Diseases) began collaborating to find out why.

However, the team faced many challenges working with SARS-CoV-2 in a biosafety level three facility. In such a high biosafety level facility, there are strict rules about what can and cannot be taken in and out of the laboratory. The team had to get creative with ways to measure contractility of the human engineered heart tissues without a recording video microscope. Using a simple camera, a monitor on a conventional microscope, a selfie stick, and some novel software written by Greenberg himself, the team showed that stem cell-derived cardiomyocytes can be infected with SARS-CoV-2 which causes them to decrease contractility similar to what is seen in failing heart tissue.

“It was a great project to get involved with, and a fantastic collaboration because we had three groups with three very different areas of expertise,” Greenberg said. “I think we were able to come together and do something really cool.”

Their work, entitled SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis, is currently available as a preprint on bioRxiv. Greenberg looks forward to continuing to do research on the cusp of cellular biology and physics to explain human health.

“Cells are at the point where we can manipulate them and do a lot of things that [in the past] we could only study biochemically in vitro,” Greenberg said. “We can test mechanistic hypotheses about these complex systems from single molecules to higher order levels of organization.”

Outside of the lab, Greenberg enjoys spending time outdoors with his four children, learning about the forces behind the weather such as tornadoes and hurricanes, and playing heavy metal music on his guitar. In addition, he loves to cook.

“There are a lot of similarities between cooking and doing wet lab; however, cooking has a much higher frequency of success,” Greenberg said.

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For over 70 years, the anticoagulant Warfarin has been a first line defense used to treat and prevent heart attacks, strokes, and other cardiovascular diseases. Warfarin inhibits the Human Vitamin K Epoxide Reductase (VKOR) to hinder coagulation. However, despite being the most popular prescribed anticoagulant, Warfarin has a very narrow range of efficacy and overdose often induces severe, sometimes fatal bleeding. In older adults, one-third of hospitalization for adverse drug reaction are due to warfarin use. (more…)

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Snapshot of a Scientist

As a five-year-old child, Dr. Linda Pike explored the cellular world through the eyepiece of a microscope and learned about chemical reactions involved in photo film development. Her lifelong love of chemistry was influenced by her father, a chemical engineer, who had Linda memorizing chemical names and symbols before kindergarten. At a very young age, Pike was destined to be a scientist.

“My father did photography as a hobby, and he used to take us down to the dark room with him,” Pike said. “We would watch the film develop and then the pictures coming up out of the dark. It was like magic.”

From the time she finished high school, she was driven to study the interface of biology and chemistry. A few years into her undergraduate education in chemistry at the University of Delaware, Pike set her goals on obtaining her PhD and becoming an academic professor. And that is exactly what she did.

She went on to obtain her PhD in biochemistry at Duke University and study -adrenergic receptors under the mentorship of Nobel Laureate Dr. Bob Lefkowitz as one of his first graduate students. This experience was the start of her lifelong interest in hormone receptors.

After earning her PhD, she moved to Seattle to start a postdoctoral fellowship with Nobel Laureate Dr. Ed Krebs at the University of Washington. She remembers her first day vividly as it was the day Mount St. Helens erupted. Years later, this eruption is still described as the most disastrous volcanic eruption in US history. The eruption column, consisting of ash and rock fragments, rose more than 15 miles into the air above the volcanic vent and deposited ash in 11 US states and two Canadian provinces.

“When I was on the plane to Seattle, we had to detour around the ash cloud from Mount St. Helens, and I remember flying by and seeing the rising ashes,” Pike said.

However, this experience did not deter her from doing seminal work on protein phosphorylation and hormone receptors during her postdoctoral training. After the completion of her postdoctoral fellowship, Pike started her own lab that focuses on the structure-function relationships of the epidermal growth factor receptor (EGFR) and its signaling cascade. She studies the canonical outside-in signaling that occurs after ligand binding but is also interested in the less well characterized inside-out signaling phenomena that cells use to adjust their signaling potential.

Pike’s work on the structure-function relationship of the EGFR and other hormone receptors throughout her career is the kind of basic science that fuels drug development used for treatment of hormone-sensitive cancers.

When asked how her work contributes to the broad field of medicine she said, “I do basic research. It is similar to when your car breaks down, and your mechanic needs to know how a car works when it’s fully functional so that they can diagnose the problem. I’m interested in figuring out how things work when they’re working normally, and that is going to enable us to intervene when things go wrong.”

Pike has not only made contributions to science, but she has been committed to mentoring young and aspiring scientists from the beginning of her professorship. In 1990, Pike along with a few other female scientists, bravely founded the Academic Women’s Network at Washington University in St. Louis as a liaison between the administration and female faculty. This organization was the first to raise awareness of the pay gap between male and female faculty. Pike’s actions empowered the organization to lobby for accessible day care, family leave, and mentorship. Over 30 years later, this organization still provides networking and training opportunities to developing female scientists.

Pike has also been committed to training the next generation of scientists in the classroom. She has been awarded the Distinguished Service Teaching Award by the medical students for 27 consecutive years, which she credits to understanding and catering to her audience.

“I just want other people to understand biochemistry so that they too can see how cool it is,” Pike said.

Pike learned many lessons as she rose through the ranks at Washington University in St. Louis. However, two stuck out as the most important: speak up and network across departments.

“One of my lessons is to speak up not only with respect to issues like we did with the Academic Women’s Network, such as pushing for pay equity, daycare, and mentoring; also speak up within your department,” Pike said.

Nevertheless, at the end of the day, Pike still loves generating data and working at the bench. She is a true lifelong scientist and always seeks to make new discoveries.

“I love sorting through data and trying to put the puzzle together,” Pike said. “What is fun about science is that you get little pieces of a puzzle, and then you have to figure out how they fit into the big picture.”

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Written by Marissa Locke, 20 July 2020

Ms. Locke is a fourth-year graduate student in the Immunology program. She is completing her thesis work in the laboratory of Dr. Deborah Lenschow.

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Illuminating the Invisible: The Soranno Lab’s Study of APOE4 Conformations

Alzheimer’s disease is a ruthless, progressive neurodegenerative disease that induces memory loss and neuronal death in patients. With more than 3 million new cases each year in the United States alone, this disease likely plagues someone you know. Despite extensive research efforts, there is no cure for Alzheimer’s disease. However, using a new high-tech approach, the Soranno lab may have a new way to elucidate part of the disease from the inside out. (more…)

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“Life began with little bags of garbage,” proposed the physicist Freeman Dyson. “Membranes made of oily scum […] enclosing volumes of dirty water containing miscellaneous garbage.” Billions of years of evolution have shaped cell membranes from simple “bags” into complex and finely-tunable structures. The cell membrane is not just a barrier separating the chaotic extracellular environment from the controlled intracellular space; they allow for the storage of electrical and chemical potential energy, facilitate transport of substances into and out of the cell, and change the cell’s shape according to its biological needs. (more…)

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When Greg Bowman presents a slideshow about the proteins he studies, their 3D shapes and folding patterns play out as animations on a big screen. As he describes these molecules, it might be easy to miss the fact that he can’t really see his own presentation, at least not the way the audience does.

Bowman, PhD, an assistant professor of biochemistry and molecular biophysics at Washington University School of Medicine in St. Louis, is legally blind. He also now leads one of the largest crowd-sourced computational biology projects in the world. The effort is aimed at understanding how proteins fold into their proper shapes and the structural motions they undergo as they do their jobs keeping the body healthy. Proteins are vital cellular machinery, and understanding how they assemble and function — or malfunction — could shed light on many of the most vexing problems in medical science, from preventing Alzheimer’s disease, to treating cancer, to combating antibiotic resistance. (more…)

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Carl Frieden was born and raised in New Rochelle, New York. He obtained his B.A. degree from Carleton College and his Ph.D. in Chemistry from the University of Wisconsin under the mentorship of Robert A. Alberty. In 1955, Dr. Frieden joined the Department of Biological Chemistry at Washington University School of Medicine as a postdoctoral fellow to work with Dr. Sidney Velick. He was hired by Carl Cori as an Instructor in 1957 and promoted to full professor in 1967. Dr. Frieden has served both as Interim Head (from 1987 to 1990 and from 1997 to 2000) and Head (from 2000 to 2005) of the Department. Among other awards, he has received the Carl and Gerty Cori Faculty Achievement Award and the Second Century Award from Washington University. He has also been awarded the Peter Raven Lifetime Achievement Award from the St. Louis Science Center as well as the Christian B. Anfinsen Award from the Protein Society. He was elected to the National Academy of Sciences in 1988 and to the American Academy of Arts and Sciences in 2004. From 1995-2000 he was an Alumni Endowed Professor and, from 2000 to 2005, the Wittcoff Endowed Chair of the Department of Biochemistry and Molecular Biophysics. He served as Director of the Medical Science Training Program (MSTP) from 1986-1991. (more…)

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Stepping into Elliot Elson’s lab is like falling into the rabbit hole in Alice in Wonderland. There are movable amplifiers perched precariously on a sled of steel runners, lasers in black boxes, pieces of salvaged equipment, cords and cables spewing like spaghetti from another machine, and a huge black tent that looks like it was inspired by Darth Vader. This is a workshop for scientific invention. The tunnel burrows deeper into the natural world’s mysteries. The elusive White Rabbit entices us to follow and to probe the enigmas of life. Elliot Elson seeks to understand and characterize cells and tissues as physical entities. His “white rabbit” has led him to adventures and discoveries that have yielded new insights into the inner workings of life itself—in several different key fields. (more…)