Article by Cristy Lytal

Video by Little Pictures

How do fingers become fingers and not toes? How does the brain generate the correct number of neurons? How do the kidneys branch into the complex and elegant structure that filters the blood and regulates its pressure?

Renowned biologist Andy McMahon spent decades unlocking these and other mysteries of embryonic development by identifying the role of key regulatory genes. By the time he decided to leave Harvard University for USC, he was ready to take on a new challenge: finding cures for patients with kidney disease.

“I felt like I could figure out how to do things that were interesting,” said McMahon. “Could I figure out how to do things that were relevant?”

With support from a $5.7 million Research Leadership Award from the California Institute for Regenerative Medicine (CIRM), McMahon headed west to find new ways to repair and regenerate the kidney.

One in 10 adults in the U.S. — more than 20 million people — are suffering from some degree of chronic kidney disease. Kidney transplants offer a hope for cure, but thousands of patients die each year due to a shortage of donor organs. Even patients who are lucky enough to receive transplants run the risk of their immune systems rejecting the donor kidneys, and they have to take immunosuppressive drugs with serious side effects for the rest of their lives.

Vito M. Campese, professor and chair of the Keck School of Medicine of USC’s nephrology division, underscores the need to find novel stem cell-based therapies for these patients.

“Despite enormous progress made in the last 50 years, as of today, we do not know the causes of many kidney diseases and how to best treat them,” said Campese, who also chairs the Medical Scientific Advisory Board of the University Kidney Research Organization (UKRO), a Los Angeles-based nonprofit group that recently established the USC/UKRO Kidney Research Center at the Keck School.

As a member of UKRO’s Medical Scientific Advisory Board and medical director of USC’s Kidney-Pancreas Transplant Program, Yasir Qazi can easily envision how stem-cell based therapies could help the patients he treats every day.

“We are looking to partner with Andy McMahon to improve and take the clinical experience of an organ transplant recipient to a completely new level,” he said.

UKRO founder Kenneth Kleinberg, who received a kidney transplant in 2007, added: “If we are to lift the scourge of kidney disease and the staggering financial burdens it imposes, the answers lie in research.”

The promise of such research is to usher in the era of regenerative medicine, which uses the power of stem cells to restore the function of damaged tissues or organs.

As the director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, McMahon is encouraging colleagues across USC to follow his lead in discovering new regenerative therapies for a broad array of diseases.

To this end, he recently recruited three stellar young faculty members: Justin Ichida; Rong Lu; and Min Yu.

Ichida is leading the USC stem cell research center’s newly opened Choi Family Therapeutic Screening Facility, where scientists can test potential drugs on reprogrammed stem cells from patients.

An expert in neurodegenerative diseases, Ichida is conducting some of the facility’s first screens — testing drug-like compounds on motor neurons formed by directly reprogramming skin cells from patients with Lou Gehrig’s disease. If one of these compounds keeps the motor neurons alive in the petri dishes, it may also keep them alive in the patients.

As a postdoctoral scholar at Harvard University, Ichida laid the foundation for his current research by helping identify new ways to make induced pluripotent stem (iPS) cells.

“I just want to do something that really changes people’s lives,” he said.

Lu’s research is equally transformative: her studies of what makes one blood stem cell outcompete another have ramifications for improving bone marrow transplants and preventing blood cancers.

As a postdoctoral scholar at Stanford University, Lu came up with the idea of “barcoding” individual blood stem cells by labeling them with a genetic marker. This allows her to observe individual cells’ behavior, interactions, self-renewal or differentiation, and contributions to forming blood.

“The most important reason I came to USC is the people here,” said Lu. “The stem cell department is growing, and everybody’s having new ideas and really being interactive and collaborative. You can feel the energy here.”

This dynamic, multidisciplinary research environment also attracted Yu, whose research focuses on finding new cures for breast cancer. Recruited in conjunction with the USC Norris Comprehensive Cancer Center, Yu filters out circulating breast cancer stem cells from billions of other blood cells to understand how the disease spreads and stop it in its tracks.

Yu did her postdoctoral work at Massachusetts General Hospital (MGH) in the lab of Daniel A. Haber, MD, PhD, who was collaborating with clinicians and bioengineers to study circulating tumor cells, which enter the bloodstream and metastasize at distant sites.

“Our director Andy McMahon also has a vision of uniting the bioengineering and medical fields, and applying basic science to clinical science,” she said. “He’s very passionate about helping young faculty start their labs and set up collaborations, so I’m excited to join.”

Also new to the center is senior faculty member Neil Segil, who is working to regenerate inner ear cells to treat hearing loss and balance disorders, which affect more than half of all adults in the U.S. by the time they reach retirement age.

To achieve this goal, he studies the developmental processes that shape the complex structures of the inner ear, the mechanisms that allow for the lifelong survival of inner ear cells, and the damage caused by noise, certain antibiotics and chemotherapy.

“Since arriving at USC, I’ve had the opportunity to collaborate with investigators with different kinds of expertise and who have not previously worked together,” Segil said. “This kind of cross-fertilization is very stimulating.”

These and the next wave of recruitments already underway will benefit from a $2 million gift from The Eli and Edythe Broad Foundation. The gift establishes the Broad Fellows Program, provides seed funding to early stage research initiatives and supports the stem cell research center’s state-of-the-art facilities in imaging, therapeutic screening, flow cytometry, and stem cell isolation and culture.

McMahon is mentoring the next generation as the director of the new Department of Stem Cell Biology and Regenerative Medicine, which offers a PhD, Master of Science and undergraduate courses, the first of which was taught by McMahon for 19 students on the University Park Campus this spring. The center also hosts a unique internship opportunity for talented high school students.

To further harness the power of collaboration, McMahon leads the university-wide USC Stem Cell initiative, bringing together more than 100 faculty members from all disciplines.

As part of USC Stem Cell, Keck School Dean Carmen A. Puliafito provided $1.2 million in Regenerative Medicine Initiative (RMI) awards to three disease teams to take early steps towards stem-cell based therapies for certain forms of deafness, bone defects and pediatric leukemia.

A fourth USC Stem Cell Kidney Disease Team is advancing the synergy between different laboratories across USC. Janos Peti-Peterdi is leading monthly meeting with USC kidney researchers McMahon, Campese, Laura Perin, Alicia McDonough and others.

The interdisciplinary effort extends beyond medical research. An economic impact analysis of Proposition 71, which created CIRM to fund stem cell research, is being planned with the USC Marshall School of Business. Students from the USC Roski School of Art and Design have conducted spring coursework in the center, finding inspiration from the beauty of science in action.

In the years to come, USC will continue to shape our future as stem cell biology moves from discoveries to cures.

As McMahon explained, “I need to strongly encourage an atmosphere where people are thinking beyond the basic science and thinking about how they can take that to new therapeutic end points for regenerative medicine.”

Andy McMahon and USC Stem Cell: From discoveries to cures

Article by Cristy Lytal

Video by Ryan Ball

For years, people were throwing away cells that could bring eyesight to the blind. These dark, blackened cells looked like spots of contamination in the petri dishes in which researchers around the world were carefully nurturing highly purified colonies of human stem cells.

It took Keck School of Medicine USC scientist David R. Hinton, MD, to realize that what appeared to be specks of dirt were actually some of the key cells that enable people to see.

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Mark Humayun and David Hinton look to stem cells to bring eyesight to the blind

Article by Cristy Lytal

Video courtesy of Children’s Hospital Los Angeles

Tracy Grikscheit, MD, really has her priorities straight.

“It goes: surgery, science, skiing. That’s the order,” said Grikscheit, principal investigator with USC Stem Cell and The Saban Research Institute of Children’s Hospital Los Angeles, attending surgeon at Children’s Hospital Los Angeles, and assistant professor of surgery at the Keck School of Medicine of USC and the USC Viterbi School of Engineering.

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Tracy Grikscheit explores frontiers of surgery, science and skiing

Article by Cristy Lytal

Video courtesy of Children’s Hospital Los Angeles

For Senta Georgia, PhD, stem cell research offers a window into much more than the biology of pancreatic cells and diabetes.

“Molecular biology is elegant,” said Georgia, principal investigator at the Saban Research Institute of Children’s Hospital Los Angeles (CHLA) and assistant professor at the Keck School of Medicine of USC. “And what really moves me is that it’s simple, and it’s the underpinnings of how life actually works. It’s almost a spiritual insight into how life is put together, how it works.”

Georgia always wanted to be a scientist — although her initial interests were much bigger than molecules. As the eldest of three children growing up in the army town of Pemberton, New Jersey, she dreamt of becoming a paleontologist and remembers building a papier-mâché dinosaur with her mother. Her aspirations shifted to archeology after she learned about ancient Egypt. By sixth grade, whales and marine biology captured her imagination, but she “couldn’t put that into a broader social context for curing disease or helping people,” she said. “I also figured out that I’m deathly afraid of the idea of jumping into the ocean!”

At the same time, she would spend most summers helping out with the family business, a moving company founded by her grandfather, who also had a jazz club in Atlantic City, New Jersey. This imbued her with the entrepreneurial spirit and management savvy needed to run a lab. She cemented her work ethic during her unusual summer jobs at two theme parks.

“I was Bert and Cookie Monster at a theme park called Sesame Place, and then I was also Bugs Bunny and Wile E. Coyote at a Six Flags another summer,” she said. “At Six Flags, you’d get these rowdy — sometimes they’re drunk, sometimes they’re just testosterone-filled — boys, who want to come and wrestle with the costume characters and take pictures and pull on you. But Sesame Place — where you’re with kids, and they love you, and you just take pictures — that was great.”

She discovered genetics when her ninth-grade class took a field trip to a company that was developing sequencing technology to advance the human genome project.

She arrived at Stanford University with the intention of studying genetics, only to discover that she found it, in her words, “really boring.” Luckily, molecular biology was a different story.

She gained valuable experience working in the labs of Stephen Houser, PhD, FAHA, at Temple Medical School and Daria Mochly-Rosen, PhD, at Stanford University, and earned her bachelor of science in Biological Sciences with a minor in Ethics in Society. As part of her minor, she explored how it would disrupt the idea of fair equality of opportunity if parents elected genetic enhancements for their children. She was one of 12 students in her graduating class to write theses and graduate with honors in two departments.

After graduation, she worked for two and a half years as a research technician in the lab of Anil Bhushan, PhD, who was studying pancreatic development at Children’s Hospital Los Angeles.

Georgia was so captivated by the project that she decided to work with Bhushan as a PhD student and eventually follow him to UCLA. She completed her dissertation about the differentiation, self-renewal and regeneration of beta cells — pancreatic cells that produce, store and release insulin, which lowers blood sugar concentrations.

She accepted a postdoctoral fellowship and assistant adjunct professorship at UCLA’s Larry L. Hillblom Islet Research Center. Over time, she became increasingly interested in questions of how undifferentiated cells become and remain beta cells.

Beta cells don’t replicate easily: current estimates are that they last between five and 20 years. This fact drove Georgia’s curiosity about intestinal stem cells, which continuously replace themselves. She received a Mentored Research Scientist Development Award (K01) from the National Institutes of Health (NIH) and studied endocrine cell differentiation in the intestines with UCLA’s Martín Martín, MD.

Her study inspired the project that currently occupies her lab at Children’s Hospital Los Angeles: trying to induce intestinal stem cells to make insulin. The ultimate objective is to use these cells to treat both Type 1 and Type 2 diabetes.

“The things that could happen in my lab could some days be exhilarating, because I’m the only person in the world that knows this,” said Georgia. “And we have a goal that we’re working towards. We might really be interested in the science and the biology of it, but in the bigger picture, we are interested in helping people, and so that means a lot.”

Senta Georgia imagines intestinal cells that make insulin

Video by Ryan Ball
Article by Cristy Lytal

USC is pleased to offer the first master’s program in stem cell biology and regenerative medicine in California.

“The program gives students a unique entrée into the rapidly expanding field of stem cell biology in the globally-recognized capital of stem cell science, California,” said Henry Sucov, PhD, director of the master’s program.

Offered by the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, the one-year program with an invitational second research year will welcome its inaugural class in Fall 2014.
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USC launches California’s first master’s program in stem cell biology

Welcome

Welcome to USC Stem Cell, a university-wide initiative connecting researchers and highlighting the latest news in regenerative medicine across USC.

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July 17, 2014

USC, UCLA and UCSF put their heads together to find stem cell-based cures for craniofacial defects

Human skull with sutures (Public domain image courtesy of Gray's Anatomy)

Human skull with sutures (Public domain image courtesy of Gray’s Anatomy)

By Cristy Lytal

One in every 2,000 babies is born with a skull that can’t grow normally. Various sections of these babies’ skulls are fused together at joints called sutures, constricting the developing brain and disrupting vision, sleep, eating and IQ. For these young patients, risky skull-expanding surgeries become an almost annual event.

Now, three leading universities for stem cell research — the University of Southern California (USC); the University of California, Los Angeles (UCLA); and the University of California, San Francisco (UCSF) — have joined forces to find better solutions for these and other patients with craniofacial defects.

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July 17, 2014

PIBBS boasts stellar new class of students

(Photo courtesy of USC)

(Photo courtesy of USC)

Lured to USC by the Programs in Biomedical and Biological Sciences (PIBBS) — the gateway into PhD programs in biomedical and biological sciences — 30 new PhD students will call the Health Sciences Campus home this fall as they begin working towards their biomedical doctoral degrees.

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July 10, 2014

USC Stem Cell researcher targets the “seeds” of breast cancer metastasis

Circulating tumor cells

Circulating tumor cells from the blood of a breast cancer patient (Image by Maria C. Donaldson and Min Yu)

By Cristy Lytal

For breast cancer patients, the era of personalized medicine may be just around the corner, thanks to recent advances by USC Stem Cell researcher Min Yu and scientists at Massachusetts General Hospital and Harvard Medical School.

In a July 11 study in Science, Yu and her colleagues report how they isolated breast cancer cells circulating through the blood streams of six patients. Some of these deadly cancer cells are the “seeds” of metastasis, which travel to and establish secondary tumors in vital organs such as the bone, lungs, liver and brain.

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