From offering new cancer-fighting options to re-growing damaged organs and nerves, regenerative techniques have a use in nearly every area of medicine.

These diverse applications are explored in the new book, “Stem Cells, Tissue Engineering and Regenerative Medicine,” edited by David Warburton, MD, director of developmental biology and regenerative medicine at the Saban Research Institute of Children’s Hospital Los Angeles (CHLA), and published by World Scientific.

David Warburton

The book features chapters by scientists from CHLA and USC, as well as from colleagues worldwide. These field leaders discuss key concepts and new developments, offering comprehensive insight into the current state of stem cell biology and regenerative medicine research.

“The book addresses some of the big questions faced by researchers in the field of stem cell biology and regenerative medicine,” said Warburton, who is also professor of pediatrics and surgery at Keck School of Medicine of USC.

“Those of us working in this field in California are positively impacted by the critical funding provided by the citizens of the state through the California Institute for Regenerative Medicine (CIRM),” Warburton said. “I believe this book shows that the hope behind CIRM — the hope that stem cells can really revolutionize medicine and human health — is fully justified.”

For more information , go to WorldScientific.com

— Debra Kain

During a lunchtime talk, Keck School of Medicine of USC Dean Carmen A. Puliafito, MD, MBA, speaks about his career and offers advice to medical students. The Jan. 28 event was sponsored by the Student Ophthalmology Interest Group of the Keck School. Ophthalmology SIG President Alex Solomon, seated at left in front row above, introduced the dean to the crowd of more than 50 students who attended.

One of her father’s many fine qualities was that he had a great eye for people, explained Bertha Gonzalez. And although he chose Giselle Petzinger, MD, to be his physician because of her top reputation, he came to admire her professionalism with patients and respect the contributions she hoped to make to the understanding of Parkinson’s disease.

Roberto Gonzales

For this reason, Roberto Gonzalez’s family chose to honor his memory by establishing the USC Roberto Gonzalez Parkinson’s Research Fund. A $1.5 million contribution will further Petzinger’s research on the effect of exercise on patients with Parkinson’s. Petzinger, an assistant professor of research in the Department of Neurology at the Keck School of Medicine of USC, has been studying which types of exercise are most efficient for keeping the symptoms of Parkinson’s disease at bay.

Petzinger said she was thrilled to receive the gift from the Gonzalez family because it will further her research, and because it came from a patient with whom she had a special bond. “He was a big believer in leading a healthy lifestyle,” said Petzinger. “We shared a common bond in wanting a deeper understanding of the connection between health and lifestyle.”

Petzinger added that Gonzalez understood that her research project is both costly and detailed. It involves basic science and human trials, including putting more than 150 people through an exercise protocol designed for Parkinson’s patients. Ultimately, Petzinger and her team hope their research will lead to new therapeutics for Parkinson’s patients.

Once the research is complete, Petzinger will  share the findings with colleagues in Mexico, which was a condition requested by the family because Gonzalez was concerned about the lack of support and good medical care for Parkinson’s patients in Mexico. Petzinger noted that Gonzalez is widely known and much-loved throughout Mexico because of his philanthropic work, which will continue through the family foundation.

“It was something he spoke about before he died,” said Bertha Gonzalez, “and it is something we agree needs to be addressed in Mexico.”

— Hope Hamashige

For the first time, Keck Medicine of USC cancer researchers at the USC Norris Comprehensive Cancer Center have traced the origins of colorectal cancer cells, finding important clues to why tumor cells become “good” or “bad,” with the potential of stopping them before they start.

The scientists employed a “Big Bang” model of human colorectal cancer growth similar to the theory that the universe started from a single point and exploded outward. The team was led by Keck faculty researchers Darryl Shibata, MD, professor of pathology at Keck School of Medicine of USC, and Christina Curtis, PhD, assistant professor of medicine and genetics at Stanford University and an adjunct assistant professor in Preventive Medicine at Keck School of Medicine of USC.

Darryl Shibata, professor of pathology.

“It’s like going back in time,”  Shibata said. “The history of each tumor is written in its genomes. To prevent tumors, you want to see what happened early on and how to stop their first cell divisions.”

By taking samples from opposite sides of colorectal tumors, the researchers reconstructed the first few divisions, which took place when the nascent tumors were too small to detect. The tumor starts were abnormal — with a burst of new mutations. Even from the start, many cancer cells expressed the abnormal mobility (or intermixing of cells) that would allow them to eventually invade and metastasize in the body. By contrast, tumor cells destined to form benign adenomas did not intermix, indicating that some tumors are born to be bad.

Understanding which tumors will kill and which ones are harmless is critical for patients to make informed decisions about tumor removal and surgery, Shibata said.

The next step is to explore what happens at the genesis of tumor cells, which Shibata and Curtis are currently studying. Curtis will also look into whether other cancers behave the same way as colorectal cancers.

The research, “A Big Bang model of human colorectal tumour growth,” is in the Feb. 9 issue of the peer-reviewed journal Nature Genetics.

Other USC researchers on the study include Andrea Sottoriva (now at the Institute of Cancer Research), Zhicheng Ma (now at Stanford University), Matthew P. Salomon, Junsong Zhao, Paul Marjoram, Kimberly Siegmund and Michael F. Press. Researchers from the CHA Bundang Medical Center at UC San Francisco and from Queen Mary University of London also contributed to the research.

— Leslie Ridgeway

USC President C.L. Max Nikias delivered his 5th annual address to Keck School of Medicine faculty on Feb. 10 in Aresty Auditorium. “Faculty and students determine our success,” Nikias told about 250 faculty members. “Your accomplishments define us and will continue to distinguish us.”

When Carley Eissman started dietary therapy to manage epileptic seizures, her goal was simple — play basketball. She did not know that it would change her life or the lives of the many people who now receive dietary support and education in Carley’s memory.

After Carley’s 2011 death at age 19 in an accident related to an epileptic seizure, her family founded the Carley Eissman Foundation to benefit families who were beginning to use dietary therapy to treat epilepsy.

Carley Eissman

As a teacher, Carley’s mother was not satisfied with simply raising and donating funds. “A good teacher gets on the carpet with the kids,” Lori Eissman said. “So I took that approach to my idea for a kitchen.”

Today, Lori and Carl Eissman and other family members can be found cooking for a growing audience of families affected by epilepsy in Carley’s Carb-less Kitchen, which offers monthly cooking classes in cooperation with the dietary clinic at LAC+USC Medical Center.

“One of the things we keep talking about is that food really cuts across cultures and languages, and it is a really nice vehicle for effective human communication,” said Arthur Partikian, MD, director of child neurology at LAC+USC Medical Center and a specialist in epilepsy. “So it was a really unique idea to have a kitchen cooking class to introduce the concept of food as medicine.”

Epilepsy is a neurological condition that affects the nervous system and causes recurring seizures over time. More than 2 million Americans have epilepsy, according to the U.S. Centers for Disease Control. It is estimated that one in 26 people will develop epilepsy at some point in their lives.

Despite epilepsy’s widespread impact, the Eissmans and others have noted that it receives little attention outside of hospitals and academic research centers.

“Epilepsy has a very negative stigma about it because you don’t see it … until you have a seizure, and then it’s gone again.” Lori Eissman said. “There are so many people who never saw that Carley had seizures. They never understood it.”

The Eissmans are doing what they can to end the stigma. “People need to talk about epilepsy like they talk about cancer or diabetes,” Lori Eissman said.

Treatments for the illness range from oral medication to brain stimulation and surgery. These treatments are often successful in controlling or even curing epilepsy, but one third of epilepsy patients live with uncontrollable seizures because no treatments work for them.

Carley Eissman was such a patient.

Laura Kalayjian, MD, chief of neurology and director of the EEG Lab at LAC+USC Medical Center, was the last of many physicians who treated Carley — but the first to suggest dietary therapy. Within a few months of strict adherence to a modified Atkins diet (MAD), Carley’s seizures had almost disappeared.

“These patients — many of them are determining whether or not to do brain surgery,” said Kalayjian, who is also an assistant professor of neurology at Keck School of Medicine of USC. “Sometimes dietary therapy is looked at as a last resort, and it shouldn’t be.”

Potential benefits to managing epilepsy through diet include weight loss and fewer negative side effects than surgery. But distinct challenges exist.

“Epilepsy is a socially isolating condition. Patients don’t have a lot of people to talk to,” said Jessica Lowe, a dietitian in the Department of Neurology who runs the dietary therapy classes. “When you put someone on this therapy, it changes their entire lifestyle, and then there are even fewer people to talk to. It’s much easier to go through it with others than to go through it by yourself.”

The teamwork aspect is important at Carley’s Carb-less Kitchen, which has seen classes double in size in just six months of operation, leading to a move to a larger location in the Wellness Center at LAC+USC Medical Center.

“It’s not like a normal cooking class where you walk away with just a recipe,” observed Lori Eissman. “It is a teaching class where families can come together for education about MAD, eat an amazing meal and walk away with a sense of community.”

Ultimately, Carley’s Carb-less Kitchen seeks to equip families with tools to master epilepsy through food. Students quickly become the masters, taking on roles as sous-chefs, bloggers and ambassadors for the modified Atkins diet.

The Eissmans started the foundation to honor their daughter and to give back to others dealing with epilepsy. But the effort is already transforming itself.

“I’m so impressed by USC and what we’ve started and how it’s grown,” Lori Eissman said.

“I know Carley would be really proud of this.”

— Ellen Gruber

Carley’s mother, Lori Eissman, at left in orange, helps conduct a recent cooking class that included Kesli Gazsi, Carley’s best friend, at right.

Three scientists from Keck Medicine of USC have won grants exceeding $4.3 million from the California Institute for Regenerative Medicine (CIRM) for research that includes creating a temporary liver for transplant patients, finding novel ways to treat immune disorders and blood diseases, and developing a new animal model for exploring diseases such as heart failure, diabetes and neurodegenerative diseases.

The grants were received by USC Stem Cell Principal Investigators Paula Cannon, PhD; Toshio Miki, MD, PhD; and Qi-Long Ying, PhD. The funds are part of the CIRM Tools and Technologies initiative, which supports projects addressing the challenges of translating stem cell discoveries into cures. The winners were chosen from 212 proposals to create, design and test the key technologies needed to usher in the era of regenerative medicine.

“Sometimes even the most promising therapy can be derailed by a tiny problem,” said Jonathan Thomas, JD, PhD, chair of CIRM’s governing board. “These awards are designed to help find ways to overcome those problems, to bridge the gaps in our knowledge and to ensure that the best research is able to keep progressing and move out of the lab and into clinical trials in patients.”

Miki’s team at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC plans to develop what he calls an “extracorporeal liver support system (ELS)” for patients with liver failure. The ELS will house a collection of human liver cells, produced from stem cells, in a device outside of the patient’s body but connected to the patient’s circulation. The ELS will therefore be able to function as a temporary liver: removing toxins, preventing irreversible brain damage, and giving the patient’s own liver a chance to recover and regenerate.

If successful, the device will allow patients to recuperate without undergoing liver transplantation.

Miki, an assistant professor of research in the Department of Biochemistry and Molecular Biology at the Keck School of Medicine of USC, received the award for his proposal “Development of a clinical-grade extracorporeal liver support system using human induced pluripotent stem cell-derived hepatic cells.” The project is an international collaboration with Katrin Zeilinger, DVM, at Charité University, Berlin, and Frank Shubert at Stem Cell Systems GmbH, with additional support from Germany’s Federal Ministry for Education and Research (BMBF).

Paula Cannon

Cannon plans to improve the precision and safety of “targeted nucleases,” which she describes as “scissors” used to edit specific genes in hematopoietic or blood-forming stem cells. Cannon hopes to develop the next generation of targeted nucleases to treat severe immune deficiencies and blood diseases, such as sickle cell disease.

Cannon and her colleagues have already developed a targeted nuclease that could potentially cure HIV/AIDS by introducing a mutation in a gene called CCR5 that confers natural immunity to HIV. Heading into clinical trials, the approach is inspired by the “Berlin patient,” a man cured of both HIV and leukemia through a bone marrow transplant from a donor with a CCR5 mutation.

Cannon — a principal investigator with USC Stem Cell and associate professor of molecular microbiology and immunology, pediatrics, and biochemistry and molecular biology at the Keck School of Medicine of USC — received the award for her proposal “Site specific gene editing in hematopoietic stem cells as an anti-HIV therapy.”

Qi Long Ying

Ying, who is also at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, plans to use stem cell-based technology to create genetically modified laboratory rats for research into new therapies for heart failure, diabetes and neurodegenerative diseases.

Transgenic rats will provide an even more powerful tool than transgenic mice, which for nearly 25 years have allowed scientists to study and model a wide range of diseases that also occur in humans. The rat is widely accepted as more similar to the human in its physiology, which is essential for cardiac, metabolic and neurological studies.

An associate professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC, Ying received the award for his proposal “Embryonic stem cell-based generation of small animal models for assessing human cellular therapies.” He is collaborating with USC colleagues Justin Ichida, PhD; Bangyan L. Stiles, PhD; and Ching-Ling (Ellen) Lien, PhD, who is also affiliated with The Saban Research Institute of Keck Medicine of USC-affiliated Children’s Hospital Los Angeles.

“At USC, we are committed to developing the critical tools and technologies for the broader scientific community to translate stem cell discoveries into patient cures,” said Andy McMahon, PhD, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, and chair of the department and university-wide initiative in stem cell research. “We are grateful for this ongoing support invested in CIRM by the voters in California. Their investment is accelerating the progress of scientists at USC and other world-class universities within the state toward the future of regenerative medicine.”

— Cristy Lytal

The Keck School of Medicine of USC climbed 30 spots in two years to join the country’s 10 highest funded medical schools by the National Institutes of Health (NIH) for 2014 otolaryngology research, according to an independent analysis by the non-profit Blue Ridge Institute for Medical Research.

John K. Niparko

In 2014, the Department of Otolaryngology – Head and Neck Surgery received $3.25 million of $85 million in NIH awards targeted to clinical otolaryngology departments across the country, vaulting to No. 10 of NIH-funded programs and surpassing the likes of Harvard University, New York University and UC San Francisco. An additional $2.8 million in NIH funding was transferred to the department in 2014 from other institutions’ existing research programs now at USC.

The achievement aligns with USC President C. L. Max Nikias’ charge to become Southern California’s most elite health system, with global prominence in medicine, biological sciences, translational research, biotechnology and patient care.

“The vibrant academic community of scientists interested in the communication sciences at USC enabled us to attract top-notch research programs from the House Research Institute, the University of Michigan and Johns Hopkins University over the last two years, providing a critical mass of investigators dedicated to the communication sciences and placing us among the world’s elite clinical otolaryngology departments,” said John K. Niparko, MD, professor and chair of otolaryngology at the Keck School of Medicine of USC. “This talented team has found important synergies at USC, and their research promises to directly affect clinical assessment and care in the immediate future.”

Niparko, an internationally renowned otoneurologic surgeon and researcher, came to USC from Johns Hopkins in February 2013, bringing with him more than $2.5 million in NIH and foundation grants that year alone. The department has grown since, adding 16 full-time faculty clinician-scientists and basic scientists, including seven who serve as principal investigators on NIH-supported studies.

NIH-funded hearing research programs at USC include the study of genetic predispositions to age-related hearing loss, exploring stem cell therapy for restoring hearing loss and evaluating the effectiveness of cochlear implantation and auditory brainstem implants in deaf children. USC’s otolaryngology department came in at No. 16 in 2013 and at No. 40 in 2012.

Otolaryngologists are physicians who diagnose and manage diseases of the ear, nose, sinuses, voice box, mouth and throat, as well as structures in the neck and face. The NIH is the largest source of funding for medical research in the world.

The Blue Ridge Institute for Medical Research used the Research Portfolio Online Reporting Tool from the NIH to compile its analysis. In 2014, USC also ranked in the Top 10 NIH-funded programs in public health and preventive medicine (No. 1) and ophthalmology (No. 3).

— Alison Trinidad

A multi-institutional team of hearing and communication experts led by the Keck School of Medicine of USC is breaking sound barriers for children born without a hearing nerve in a clinical trial backed by the National Institutes of Health (NIH).

Launched in March 2014, the three-year study has enrolled five of 10 participants and successfully implanted an auditory brainstem implant (ABI) device in four children who previously could not hear.

The research team is presenting preliminary findings at the American Association for the Advancement of Sciences (AAAS) 2015 Annual Meeting in San Jose, California, on Feb. 14.

“Initial activation of the ABI is like a newborn entering the world and hearing for the first time, which means these children will need time to learn to interpret what they are sensing through the device as ‘sound,’” said audiologist Laurie Eisenberg, PhD, a Keck School of Medicine of USC otolaryngology professor and study co-leader. “All of our study participants whose ABIs have been activated are progressing at expected or better rates. We are optimistic that, with intensive training and family support, these children will eventually be able to talk on the phone.”

Hearing loss manifests in various forms, most of which can be partially restored through hearing aids and cochlear implants. Those devices cannot help a small population of individuals who do not have a cochlear, or hearing, nerve — these people are unable to perceive sound, no matter how loud, outside of feeling vibration. The ABI is considered revolutionary because it stimulates neurons directly at the human brainstem, bypassing the inner ear entirely.

Surgeons outside the United States have been doing ABI surgeries in children for more than 10 years, but there was never a formal safety or feasibility study under regulatory oversight. In the United States, the ABI is approved for use only in patients 12 years or older with neurofibromatosis type II, an inherited disease that causes a non-malignant brain tumor on the hearing nerve, but it has shown limited effectiveness in adults.

Scientists believe that the ABI would be more effective in younger children, when their brains are more adaptable. The clinical trial will attempt to prove that the surgery is safe in young children and allow researchers to study how the brain develops over time and how it learns to hear sound and develop speech.

“Hearing loss can be devastating to a child’s social development, and for some children, the ABI is their last viable chance to hear,” said Keck School of Medicine of USC Professor Robert V. Shannon, PhD, an investigator for the trial and a leading scientist in the development of ABI technology since 1989. “Several of the young children who had ABIs implanted outside the United States have sought help at the USC-CHLA Center for Childhood Communication and we know that they now have the potential to understand speech. This really shows how powerful and flexible the brain is. By studying how the brain and the hearing system work together through this device, our team will set the gold standard for use of this technology.”

The NIH clinical trial grant U01DC013031 covers the costs of the device, procedure and subsequent testing. To qualify for participation, patients aged 2 to 5 years old must show that standard treatment such as hearing aids and cochlear implants have been ineffective.

— Alison Trinidad

Emeritus Professor Shaul G. Massry, MD, will be awarded the Distinguished Faculty Award and two graduates of the Keck School of Medicine of USC will be awarded alumni awards at the second Keck Scholarship Gala on Saturday, March 7, at Town & Gown on the University Park Campus.

The annual celebration of donors and students who have received medical scholarships in 2014 and 2015 also serves as a fund-raiser to support medical scholarships. Last year, more than 250 people attended and almost $325,000 was raised.

“We are pleased to honor our generous supporters with this event,” said Carmen A. Puliafito, MD, MBA, dean of the Keck School. “Having the ability to offer medical scholarships helps the Keck School attract the most promising future physicians and researchers, and launch them on careers to save lives and advance medicine as tomorrow’s health care leaders.”

Massry is the former chair of nephrology at Keck School of Medicine of USC and president of the Meira and Shaul G. Massry Foundation, which awards the Massry Prize to recognize outstanding contributions to the biomedical sciences and the advancement of health. Twelve recipients have gone on to receive Nobel Prizes.

Tony Alamo

Antonio T. Alamo, MD, a 1991 graduate of Keck School of Medicine of USC, will receive the Alumni Service Award.

He runs a private internal medicine practice in Las Vegas and is chairman of Nevada’s gaming commission. Alamo has served as chief of staff of two Las Vegas hospitals and founded Alamo Medical Clinic. His award will recognize 16 years as a volunteer physician for the Las Vegas Metropolitan Police Department.

Alamo’s service during a hostage barricade situation in 2006 previously earned the police Medal of Unit Valor.

The recipient of the Distinguished Alumni Merit Award is J. Mario Molina, MD, who earned his USC medical degree in 1984. He is president and CEO of the Fortune 500 company Molina Healthcare, Inc., which serves more than 6.6 million beneficiaries of Medicaid and Medicare in 17 states and two U.S. territories.

MARIO MOLINA

Molina previously received the E&Y Greater Los Angeles Entrepreneur of the Year Award and was featured in Time magazine as one of the 25 most influential Hispanics in America in 2005.

For details about the gala, contact Connie Wagner at (213) 821-7080 or crwagner@usc.edu. Tickets may be purchased at keck.usc.edu/ScholarshipGala.

— Sharon Brock

It sounds like something straight out of science fiction: Robots zap danger surrounding them.

But for Keck Medical Center of USC, the new devices are powerful tools in the fight against the spread of disease and infection.

Xenex ultraviolet robots, which stand about five feet tall and emit pulses of ultraviolet light to render bacteria and viruses inactive, were recently deployed in Keck Hospital of USC and USC Norris Comprehensive Cancer Center.

Medical center officials said the new technology is an important tool to provide safe, sterile environments for patients and staff members.

“My interest was in reducing infection rates, especially for bacteria that are hard to manage,” said Chief Medical Officer Stephanie Hall, MD.  “This provides a new level of disinfection that we could not normally achieve.”

Manufactured by San Antonio-based Xenex Disinfection Services, the robots are used by more than 300 U.S. hospitals.

Pathogens can pose significant health risks, and disinfection of hospital surfaces is crucial for patient safety. About 1 in 25 U.S. hospital patients have had a healthcare-associated infection, according to the Centers for Disease Control and Prevention.

Xenex robots use powerful pulses of Xenon-based ultraviolet light that penetrate cell walls of bacteria and viruses, making them no longer infectious. The UV-C light can kill pathogens such as Ebola, measles, VRE, c. difficile, MRSA and mold.

Purchase of a Xenex robot for Keck Hospital and USC Norris was made possible by gifts from Paula Hsu and her family in appreciation for the extraordinary care that her mother received.

“Our family is forever grateful to Dr. Stephanie Hall and especially Dr. Glen Ault for the care rendered to my mother at the hospital a few years ago,” Hsu said. “Today, at 94, she is well and sound.  When Dr. Hall mentioned this new disinfecting equipment to us, we felt privileged to be able to show our gratitude by contributing.”

Staff members underwent training with the Xenex robot after it arrived Feb. 17 at Keck Hospital of USC.

“This enhances the level of disinfection we’re able to provide,” said Infection Preventionist Angie Ghanem.

A Xenex robot has been in use since December at the Center for Cystic Fibrosis. It was purchased with financial gifts from the Webb Foundation and Steven Tyre, CPA, trustee of the Bob and Margrit Gold Trust.

Although brief exposure to the light is considered safe, the robots are used in unoccupied rooms and are equipped with a motion detector capable of shutting down the system if motion is detected. The UV light cannot penetrate glass, doors or plastic, nor will it damage supplies or equipment in the room being disinfected.

The robots have a simple user interface, are WiFi compatible and dispatch real-time data. They will be used in addition to regular cleaning and will provide enhanced cleaning in targeted areas of patient units and procedure rooms. A Xenex robot takes about 15 minutes to disinfect a typical patient room.

Each device costs about $90,000.

A Xenex robot is used 18 times a day in the Cystic Fibrosis Clinic, and patients have been curious about the new machine roaming the halls with staff members.

“It has increased the sense of comfort in our patients,” said Center for Advanced Lung Disease Nurse Manager Debbie Benitez, RN. “They feel we are going above and beyond what we need to do for their safety.”

— Douglas Morino

Older people who have sleep problems found more relief from a mindful meditation program than from a conventional sleep education program, Keck Medicine of USC researchers have found.

In a clinical trial of 49 people in Los Angeles 55 and older, scientists from USC and UCLA discovered that participants in a group meditation program reported better results than those given behavioral sleep education. The research indicates that focusing attention and awareness on the present moment without judgment or reacting to thoughts — as taught through mindfulness meditation — has positive effects not just on sleep but on conditions that often result from poor sleep.

“We were surprised to find that the effect of mindfulness meditation on sleep quality was large and above and beyond the effect of the sleep hygiene education program,” said David S. Black, PhD, MPH, corresponding author of the study and assistant professor of preventive medicine at Keck School of Medicine of USC.

Black, director of the American Mindfulness Research Association, concludes that “mindfulness meditation appears to have clinical importance by serving to reduce sleep problems among the growing population of older adults.”

This effect on sleep appears to carry over into reducing daytime fatigue and lessening symptoms of depression. It is estimated that 50 percent of adults over age 55 will experience sleep disturbances, which include trouble falling asleep and waking in the middle of the night. According to the National Sleep Foundation, the sleep needs of older adults do not diminish with age, and many report dissatisfaction with their sleep and tiredness during the day.

Black’s team compared the Mindful Awareness Practice (MAPs) program at UCLA, a six-week, two-hour-a-week program introducing mindfulness meditation to participants, to a so-called sleep hygiene program that provided strategies such as relaxation before bedtime, monitoring of sleep behavior and not eating before sleeping. The research was conducted via self-reported surveys.

Black’s future research will focus on combining the two methods as a means of improving sleep.

The research team includes Gillian O’Reilly, a doctoral student in the Department of Preventive Medicine at the Keck School, and Richard Olmstead, PhD,  Elizabeth Breen, PhD, and Michael R. Irwin, MD, all of UCLA.

The research was published online Feb. 16 in the Journal of the American Medical Association Internal Medicine. Funding was provided by the National Institutes of Health (NIH), National Institutes of Mental Health (NIMH), the UCLA Older Americans Independence Center, the Cousins Center for Psychimmunotherapy at UCLA, the Pettit Family Foundation and the Furlotti Family Foundation.

— Leslie Ridgeway

A new study by researchers at Children’s Hospital Los Angeles (CHLA) has shown that small intestine grown from human cells replicates key aspects of a functioning human intestine.

The small intestine they developed contains important elements of the mucosal lining and support structures, including the ability to absorb sugars, and even tiny or ultra-structural components like cellular connections.

The research was led by Tracy C. Grikscheit, MD, an assistant professor of surgery at the Keck School of Medicine of USC and a principal investigator for the Saban Research Institute of CHLA and its developmental biology and regenerative medicine program. Grikscheit is also a pediatric surgeon at Children’s Hospital Los Angeles and a principal investigator with USC Stem Cell.

Published online Jan. 8 by the American Journal of Physiology: GI & Liver, the work brings surgeons a step closer to helping human patients via this regenerative medicine technique.

Tissue-engineered small intestine, known as TESI, grows from stem cells contained in the intestine and offers a promising treatment for short bowel syndrome (SBS), a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies. TESI may one day offer a therapeutic alternative to the current standard treatment, which is intestinal transplantation, and could solve its largest challenges — donor shortage and the need for lifelong immunosuppression.

Grikscheit aims to help her most-vulnerable young patients, including premature babies who develop a devastating disease called necrotizing enterocolitis (NEC) in which life-threatening intestinal damage requires removal of large portions of the small intestine. Without enough intestinal length, the babies are dependent on intravenous feeding, which is costly and may cause liver damage.

NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing. Nearly a third of patients die within five years.

CHLA scientists had previously shown that TESI could be generated from human small intestine donor tissue implanted into immunocompromised mice.
The new study determined that mouse TESI is highly similar to the TESI derived from human cells, and that both contain important building blocks, such as the stem and progenitor cells that will continue to regenerate the intestine as a living tissue replacement. And these cells are found within the engineered tissue in specific locations and in close proximity to other specialized cells that are known to be necessary for a fully functioning organ.

“We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,” Grikscheit said.

Additional contributors from Children’s Hospital and Keck Medicine of USC include Christa N. Grant, Garcia Salvador, Frederic Sala, Ryan J. Hill, Daniel E. Levin, Allison L. Speer, Erik R. Barthel, and Hiroyuki Shimada, as well as Nicholas C. Zachos of Johns Hopkins University’s School of Medicine.

— Debra Kain

Keck Medicine of USC physicians have been awarded funding to explore the effectiveness of new non-invasive ultrasound-based techniques to screen liver transplant patients for potentially deadly disease.

This is one of the several investigator-initiated research grants secured recently by the Department of Radiology.

Edward Grant, MD, chair of the Department of Radiology, and Hisham Tchelepi, MD, chief of the ultrasound division, have received $300,000 from GE Healthcare Inc. to investigate non-invasive and quantitative ultrasound-based techniques — shear wave elastography and parametric imaging with contrast enhanced ultrasound — for assessment of liver fibrosis in liver transplant recipients with hepatitis C, which can continue to cause damage even after a patient receives a new liver.

The Department of Radiology is the first in the region to introduce these ultrasound technologies. “This adds to our spectrum of diagnostic imaging services in ultrasound,” Grant said.

New shear wave elastography technology developed by GE Healthcare received approval from the FDA in November and measures organ tissue stiffness to help identify any potential underlying fibrosis. Liver fibrosis is associated with cirrhosis and is currently assessed using needle biopsy, which is invasive and expensive.
Parametric imaging using contrast-enhanced ultrasound helps map blood flow and is another new diagnostic aid to examine the liver.

The new non-invasive techniques could allow patients to be better screened and evaluated so they can more quickly receive appropriate treatment. The three-year grant will allow 100 patients to be screened and treated.

“We will use these two new tools for evaluating patients and providing them, ultimately, with better treatment,” Grant said.

Grant was one of the pioneers in developing the clinical use of neonatal cranial sonography. Considered an international authority in ultrasound, Grant has been the chairman of the Department of Radiology since 2002.  Tchelepi was recently recruited from Wake Forrest to lead radiology’s ultrasound division. Grant and Tchelepi often speak about ultrasound at national and international venues.

— Douglas Morino

A deficiency in the protein responsible for moving glucose across the brain’s protective blood-brain barrier appears to intensify the effects of Alzheimer’s disease, according to a new study from the Keck School of Medicine of USC.

The research suggests that targeting the protein called GLUT1 could help prevent or slow the effects of Alzheimer’s, especially among those at risk for the disease. The study appeared March 2 in the online edition of the scientific journal Nature Neuroscience.

Berislav V. Zlokovic

“Our results suggest that GLUT1 deficiencies at the blood-brain barrier are not just symptoms of Alzheimer’s but, in fact, lead to a series of vascular injuries that worsen the effects of the disease,” said the study’s principal investigator, Berislav V. Zlokovic, MD, PhD, who is director of the Zilkha Neurogenetic Institute at the Keck School and the Mary Hayley and Selim Zilkha Chair for Alzheimer’s Disease. “We do not know yet whether medicine can restore GLUT1 expression, but we believe that targeting the protein may help prevent Alzheimer’s from getting worse among individuals predisposed to develop the disease.”

About 5.2 million people of all ages in the United States have Alzheimer’s disease, an irreversible, progressive brain disease that causes problems with memory, thinking and behavior. According to the Alzheimer’s Association, it is the most common type of dementia, a general term for loss of memory and other mental abilities. Alzheimer’s is projected to affect 16 million Americans over age 65 by 2050.

Glucose is the brain’s main energy source, and GLUT1 helps move it across the blood-brain barrier, a cellular layer that prevents entry of blood and pathogens into the brain. Previous research has shown diminished glucose uptake in the brain among individuals at genetic risk for Alzheimer’s disease, as well as those with a positive family history who develop the disease but show mild or no cognitive impairment.

In this new study, Zlokovic’s team used transgenic mice to show that GLUT1 is necessary to maintain proper brain capillary networks, blood flow and blood-brain barrier integrity. They found that GLUT1 deficiency led to diminished glucose uptake into the brain as early as two weeks of age and, by six months of age, neuronal dysfunction, behavioral deficits, elevated levels of amyloid-beta peptide, behavioral changes and neurodegenerative changes.

The team also found that GLUT1 deficiency in the endothelium – the inner lining of blood vessels – initiated breakdown of the blood-brain barrier. Alzheimer’s disease pathogenesis is widely believed to be driven by amyloid-beta peptide buildup in the brain, which is facilitated by a breakdown of the blood-brain barrier.

Other USC co-authors include Ethan A. Winkler, Abhay P. Sagare, Sanket V. Rege, Jesse D. Sengillo, Pan Kong, Amy R. Nelson, John S. Sullivan, Zhen Zhao, Herbert J. Meiselman, Rosalinda B. Wenby, Jacob Makshanoff and Edward Zuniga.

— Alison Trinidad

Two physician faculty leaders from Keck Medicine of USC presented their script for living longer and living better on March 5 at the 2015 USC Women’s Conference.

Leslie Saxon, MD, professor of medicine and clinical scholar, and colleague Laura Mosqueda, MD, chair of Family Medicine,  provided advice on optimal aging.

“Exercise is the most important thing you can do for brain health,” Mosqueda advised.

A prescription drug commonly used to treat age-related vision loss also reverses vision loss caused by diabetes, according to a new study led by investigators from the USC Eye Institute.

Rohit Varma

“We found that ranibizumab can save the sight of thousands of working-age individuals suffering from diabetic eye disease, as standard treatments such as laser are not as effective,” said Rohit Varma, MD, MPH, director of the USC Eye Institute, professor and chair of ophthalmology at the Keck School of Medicine of USC and the study’s lead author.

Diabetic retinopathy and diabetic macular edema are the leading causes of vision loss in working-age adults in the United States, according to the National Eye Institute. Laser surgery is the standard treatment for advanced stages of the disease, which is characterized by blurred vision, but previous research has shown that only 30 percent of patients saw improvement in their vision as a result.

Varma’s team developed a population-based model that suggests that administering 0.3 milligrams of ranibizumab every four weeks to patients with diabetic macular edema would reduce the number of cases of vision impairment by 45 percent, or 5,134 individuals, and the number of cases of legal blindness by 75 percent, or 1,275 individuals.

The model was based on the approximately 37,000 Hispanic and non-Hispanic white adults with diabetic macular edema in the United States for whom ranibizumab treatment could be used. Because other race and ethnic groups were not included in the study, the treatment may benefit even more people than the study results show.

Ranibizumab is manufactured and marketed by Genentech Inc. under the trade name Lucentis. The study published Feb. 7 in the online edition of the medical journal Ophthalmology was supported in part by Genentech.

— Alison Trinidad

Keck Medicine of USC researchers in the lab of Peggy Farnham, PhD, were key participants in the recent publication of a landmark collection of scientific papers related to mapping the DNA and histone modifications in human epigenomes and the ways that they coordinate the body’s biological activities.

Farnham is one of the leading experts in epigenetics, a field of study that seeks to explain how genes and life experience conspire to make us who we are. The epigenome is a series of chemical annotations to our DNA and associated proteins that determines whether, how and when genes are activated. These chemical changes determine normal development of the body, and disruptions in epigenetic control are involved in disorders from cancer to autism to heart disease.

Beginning in 2008, the Roadmap Epigenome Consortium set out to identify the cell type-specific regulatory elements in a large number of different human cell types, said Farnham, who is the William M. Keck Professor of Biochemistry and Molecular Biology and associate dean for graduate affairs at the Keck School of Medicine of USC. She has been part of the consortium since its inception.

The research, a culmination of years of work by hundreds of participants, was published online Feb. 18 by the journal Nature and six other journals under the aegis of Nature Publishing Group.

In all, the consortium of scientists simultaneously published 22 papers that represent the first comprehensive maps and analyses of the epigenomes of a wide array of human cell and tissue types. Farnham and her lab took part in a large integrative paper that was central to the project, plus additional papers in the set.

A unique contribution of Farnham’s lab was a paper that focuses on deleting a regulatory element to expand our knowledge of how genomic variation contributes to the risk of colon cancer. Follow-up efforts will expand the analyses to prostate cancer.

She said that publication of the epigenome mapping project has great significance in our understanding of how the epigenome modifies the genome, making marks that tell genes what to do and when to do it.

“One of the surprising findings that came from genome sequencing is that humans have about the same number of protein-coding genes as a microscopic worm,” Farnham said about prior research that formed the foundation upon which  epigenome research is based.

“Only a small fraction of the human genome encodes proteins, suggesting that the large differences between our development and that of other, less complicated organisms is likely due to precise changes in the abundance of specific proteins, which is in turn controlled by regulatory elements that can be switched from inactive to active states,” she continued.

Unlike genes, which remain fairly stable during an individual’s lifetime, the epigenome is dynamic. Researchers are finding that the epigenome’s instructions can be altered by personal habits such as smoking or eating fatty foods. It also changes in response to experiences such as prolonged severe stress. Understanding why this happens is vital to the battle against disease.

“Understanding how genomic sequence elements regulate normal development and differentiation — and how variants in the genome contribute to human diseases such as colon cancer — are leading challenges of 21st Century medicine,” Farnham said.

Publication of the research was an undertaking in itself. More than a year ago, the consortium approached Nature to propose publication of papers that represented the culmination of the Roadmap Epigenome Mapping Project.

“Nature said they were willing to consider publication of a large set of papers,” Farnham said, “and everyone sent abstracts of their individual papers. Then the various Nature journals decided if they were interested in reviewing any of them.”

Papers that made the first cut then went through the journals’ normal editorial scrutiny process. “Not all of the submitted papers were accepted,” Farnham said. “The final 22 are the ones that made it the whole way.”

In all, Farnham and members of her lab took part in four of the 22 papers that were part of the Feb 18 package. Their paper that focused on colon cancer was published in Nature Communications. Farnham said that all the research described in that paper was performed here at USC.

The Farnham Lab is situated at USC Norris Comprehensive Cancer Center. Additional USC participants in the epigenome research were Research Specialist Heather Witt, PhD candidate Lijing Yao, PhD candidate Yu Gyoung Tak and Benjamin Berman, who at that time was an assistant professor in the Department of Preventive Medicine at the Keck School of Medicine of USC.

— Les Dunseith

Medical student Shuhan He embraces his girlfriend Mary Wang after learning that he had received his first choice, Harvard Mass in Boston.

The Keck School of Medicine of USC welcomed Match Day 2015 on March 20, joining medical school seniors and other applicants across the United States who learned simultaneously where they would spend the next few years during their residencies.

Keck School students and their families and friends gathered in the Harry and Celeste Pappas Quad with their instructors at breakfast time for welcoming remarks by Keck School Dean Carmen A. Puliafito, who joined remotely from a conference he was attending in Miami. Other speakers included Donna Elliott, MD, EdD, senior associate dean for student affairs, and Henri Ford, MD, MHA, vice dean, medical education.

A private, not-for-profit corporation, the National Resident Matching Program, provides a uniform date to learn of appointments to graduate medical education positions.

Medical students Miriam Lassiter, T.C. Scotton and Branden Turner are all smiles after learning their fates on Match Day 2015.

As is customary, the students picked up their match letters beginning at 9 a.m. and opened them in the presence of friends, family members and colleagues. Within seconds, shouts of exultation echoed through campus as medical students celebrated matches with their top choices.

Harut Hovsepyan hugs friend and fellow medical student T.C. Scotton as they celebrate their results on Match Day 2015.

Almost 300 people were on hand March 7 at Town & Gown of USC to celebrate and raise funds for medical scholarships at the Keck Scholarship Gala. The event raised $290,000.

Carmen A. Puliafito, MD, MBA, dean of the Keck School of Medicine of USC, told those in attendance that their donations enable exceptional students to pursue medical studies, conduct research and assist with hands-on patient care regardless of their socio-economic circumstances.

“We can only compete to attract the best and brightest students —  men and women who will ultimately become our future residents, faculty, physicians and researchers — by offering full and partial scholarship,” Puliafito told the crowd. “Your generosity will impact not only the excellent training of our talented medical students, but also the lives of the many patients they will help throughout their careers.”

Emcee Fritz Coleman of KNBC-TV receives a plaque from Dean Carmen A. Puliafito to commemorate the event.

The event’s emcee was Fritz Coleman, longtime weathercaster for KNBC-TV in Los Angeles. Coleman has been active in charitable causes throughout his 32-year career as a local on-air personality.

Emeritus Professor Shaul G. Massry, MD, was awarded the Distinguished Faculty Award during the festivities. Massry is the former chair of nephrology at the Keck School of Medicine and president of the Meira and Shaul G. Massry Foundation, which awards the Massry Prize to recognize outstanding contributions to the biomedical sciences and the advancement of health.

Receiving the Alumni Service Award was Antonio T. Alamo, MD, a 1991 graduate of the Keck School of Medicine. He runs an in­ternal medicine practice in Las Vegas and chairs Nevada’s gaming commission.

The recipient of the Distinguished Alumni Merit Award was J. Mario Molina, MD, who earned his medical degree from USC in 1984. He is president and CEO of the Fortune 500 company Molina Healthcare, Inc.

During the event, 31 Keck School scholarship recipients were recognized by Henri R. Ford, MD, MHA, vice dean of educational affairs.
The gala also included a cocktail reception in Town & Gown’s courtyard and foyer. Sponsors of the event included Keck Medical Center of USC, the USC Institute of Urology and the USC Office of Diversity, plus several Keck School departments.

A total of 31 medical students received their scholarships during the March 7 gala at Town & Gown.