CHOC Researcher Recognized at International Molecular Medicine Conference

Jeffrey Huang, Ph.D., a research scientist at CHOC Children’s Research Institute whose scientific interests include applying innovative molecular biology techniques to the treatment of rare pediatric disorders, was recently honored at the Molecular Medicine Tri-Conference. Considered one of the world’s leading international events in the field of drug discovery, development and diagnostics, the conference attracts more than 3,000 innovative thinkers and thought leaders in biotech, pharma and academia from around the world.  In addition to serving as a guest speaker at the conference, Dr. Huang was honored with the “Best Poster” award for his presentation, “Engineering cellular and animal models of rare disease using CRISPR-Cas9 genome editing.” In this Q & A, he shares insight about his research and its promise for the future.

What inspires you to focus on rare pediatric disorders, such as Pompe disease?

As a translational research scientist, I am committed to bringing the best scientific research has to offer to the clinic. My decision to join CHOC Children’s Research Institute was fueled by a desire to address the lack of alternative treatment options for CHOC patients and families affected by rare pediatric disorders. Over 30 million Americans – nearly 1 in 10 people – suffer from one of the 7,000 conditions classified as a rare disease. Many rare disorders often lead to progressively debilitating and sometimes fatal outcomes in infants and children.  Unfortunately, there are no cures for most rare diseases; if existent, current therapy only attenuates or slows disease progression. My primary research focus is to evaluate and develop CRISPR genome editing therapeutics to address deficiencies of existing treatment for rare pediatric disorders such as Pompe disease.

Jeffrey Huang, Ph.D., research scientist at CHOC, after being honored with the “Best Poster” award for his presentation, “Engineering cellular and animal models of rare disease using CRISPR-Cas9 genome editing,” at the recent Molecular Medicine Tri-Conference.

What are you seeking to accomplish with your research?

Currently, I lead a project to develop personalized CRISPR genome editing therapeutics for Pompe disease – our proof-of-concept rare pediatric disorder. Pompe disease is a progressive cardiac and skeletal myopathy lysosomal storage disorder (LSD) which, despite intravenous doses of recombinant enzyme 40 times that of other LSD treatments, results in the deterioration of affected patients’ muscle strength.  With over 15 years of experience in advanced molecular, cellular, and developmental biology, I have outlined the following strategy to evaluate the therapeutic efficacy and safety of CRISPR genome editing for Pompe disease.

The specific aims of our project are:

1) To generate, via CRISPR-Cas9 technology, animal models of Pompe disease that bear mutations homologous to those that cause human Pompe disease

2) To fully evaluate and validate the animal models generated to ensure molecular, biochemical, histopathological and functional analogy to human Pompe disease

3) To develop specific CRISPR genome editing/delivery systems correcting mutations in validated models of Pompe disease

4) To assess molecular, biochemical, histopathological and functional efficacy as well as safety of CRISPR genome correction in our Pompe disease animal models

I am excited to report that within the past year we have successfully demonstrated that our Pompe disease-specific CRISPR genome editing strategy has produced the desired mutations in cultured cells. Following this pilot experiment, we microinjected our Pompe disease CRISPR reagents into fertilized mouse zygotes to produce the first CRISPR-generated animal model at CHOC Children’s (Specific Aim 1). We are currently expanding this new animal model of Pompe disease and will perform the appropriate tests on the expanded cohort to confirm analogy to human Pompe disease (Specific Aim 2).

Our newly generated Pompe animal models will form the basis for future studies that will test the efficacy and safety of CRISPR-mediated genome correction in an in vivo context.

What other projects are in the works?

Future work will focus on evaluating which CRISPR delivery strategy works best to correct Pompe disease mutations in affected tissue (Specific Aim 3) and assessing the efficacy and safety of genome correction in our animal model (Specific Aim 4). Our application of CRISPR technology to Pompe disease will form the basis for future personalized genome editing studies and model the appropriate safeguards that need to be taken prior to testing CRISPR genome editing therapies in a clinical setting.

Learn more about CHOC Children’s Research Institute.

CHOC Children’s Research Week 2015

Join us for CHOC Children’s Research Week, being held through Nov. 20 on CHOC Children’s main campus in Orange.

CHOC Research

Tuesday, Nov. 17

Research Resources at CHOC Children’s

8 a.m. – 9:30 a.m., Bill Holmes Tower, second floor, conference room A & B

Presenters: Amit Soni, MD, Megan Bailey, BA, Phuong Dao, JD

 

CHOC Research Institute Open House

Noon – 1:30 p.m., CHOC Research Building, third floor, conference room 2

Refreshments will be served.

 

Wednesday, Nov. 18

Research Grand Rounds

“A Closer Look at Genomics in the Diagnosis and Treatment of Pediatric Cancers”

8 a.m. – 9 a.m., CHOC West, Wade Education Center, second floor

Leonard S. Sender, MD, medical director, Hyundai Cancer Institute

Keri Zabokrtsky, MS, research programs supervisor, CHOC Children’s Hyundai Cancer Genomics Program

Troy A. McEachron, PhD, senior postdoctoral fellow, Integrated Cancer Genomics Division, Translational Genomics Research Institute (TGen)

CME credit available.

 

Scientific Poster Presentations

9 a.m. – 10 a.m., CHOC West, Wade Education Center, second floor

Moderated by Philip Schwartz, PhD, supervisor senior scientist, CHOC Children’s and managing director, National Human Neural Stem Cell Resource

 

Thursday, Nov. 19

2015 CHOC – UC Irvine Child Health Research Awardee Presentations

9:30 a.m. – 11:30 a.m., CHOC Research Building, third floor, conference room 2

Moderated by Michelle Fortier, PhD, co-director, Center on Stress & Health and assistant professor, UC Irvine School of Medicine

Presenters: Antonio Arrieta, MD, Tami John, MD, Calvin Li, PhD, Joanne Starr, MD, Sharief Taraman, MD, & Ruth McCarty, MS, LAc

Light refreshments will be served.

 

Emerging Research Programs

2:30 p.m. – 4 p.m., CHOC Research Building, third floor, conference room 1

Moderated by Brent A Dethlefs, executive director, CHOC Children’s Research Institute

Presenters: Antonio Arrieta, MD, Randy Berg, PhD, Mariella Simon, PhD Candidate, Raymond Wang, MD

Light refreshments will be served.

 

Friday, Nov. 20

Research Subjects’ Perspectives

11 a.m. – 1 p.m., Bill Holmes Tower, second floor, conference room C

Moderated by Kathleen Adlard, clinical nurse specialist, Hyundai Cancer Institute and industry track IRB co-chair

Lunch will be served.

 

Highlights in Nursing Research

1:30 p.m. – 2:30 p.m., Bill Holmes Tower, second floor, conference room B

“Coping with Cancer: The Adolescent and Young Adult Journey”

Nancy Kuntz, MN, RN, CPNP, CPON

“Nursing Evidence-Based Practice: Best Care Based on Well-Designed Studies”

Susan Elliott, PhD, RNC, APRN-BC

Light refreshments will be served.

 

For more information, please call 714-509-4341. Learn more about research services at CHOC.

2015 CHOC Children’s – UC Irvine Child Health Research Awards

We are pleased to announce that we just completed another round of the CHOC Children’s – UC Irvine Child Health Research Awards, our annual call for proposals that enhance research collaborations between CHOC and UC Irvine and further the Mission, Vision and strategic aims of the CHOC-UCI Child Health Research Strategic Plan. Intended to support research and collaboration in targeted areas of research excellence that align research strengths for focused growth and maximal translational impact, our call this year specifically solicited applications for two funding mechanisms, Pilot Collaborative Research Awards and Clinician Investigator Awards.

Child Health Research Award - UC Irvine Infographic

Pilot Collaborative Research Awards are intended to provide funds for collaborative projects in need of initial start-up funding to enable procurement of other independent support. These awards are designed to promote novel, translational research efforts that coalesce talented clinicians and researchers from CHOC and UC Irvine. Projects bring investigators from multiple disciplines from CHOC and UC Irvine together to identify targets for improved diagnosis, prevention, or treatment of a pediatric health problem relevant to the goals of the CHOC-UCI Child Health Research Strategic Plan.

Clinician Investigator Awards are intended to provide funds for clinician-investigator initiated projects in need of funding to advance study into a clinically relevant and important topic that has a high likelihood of impacting clinical practice and the positive experience of pediatric/ adolescent patients and their families. Priorities are given to proposals that are closely aligned with the research themes identified in the CHOC – UCI Child Health Research Strategic Plan. Projects identify targets for improved diagnosis, prevention, or treatment of a pediatric health problem relevant to the goals of the CHOC-UCI Child Health Research Strategic Plan. Collaborations between CHOC and UCI faculty are strongly encouraged, but not required.

This year we received 18 proposals, an increase of 13% over last year, covering a wide range of topics and specialties. After external academic peer reviews and committee discussions, we decided to fund 6 projects, 3 Pilot Collaborative Research Awards and 3 Clinician Investigator Awards.

Congratulations to the well-deserving recipients of the 2015 awards! They are listed below, in order of award type and Principle Investigator’s last name.

 

Pilot Collaborative Research Awards.

Principal Investigator: Dr. Gurpreet Ahuja

Collaborators: Drs. Nguyen PhamKevin Huoh, Naveen Bhandarkar, Carolyn Coughlan, Joon You

Project Title: NIR Imaging of Pediatric Sinuses

 

Principal Investigator: Dr. Tami John

Collaborators: Drs. Lilibeth Torno, Daniela Bota, Grace Mucci, Mary Zupanc, Jack Lin

Project Title: Cognitive Training to Promote Neuroplasticity and Neural Re-circuitry in Chemotherapy

Associated Cognitive Impairment

 

Principal Investigator: Dr. Calvin Li

Collaborators: Drs. John Weiss, Hong Yin, William Loudon

Project Title: A Tunable Engineered Tissue Graft Model for Repair of Traumatic Brain Injury

 

Clinician Investigator Awards

Principal Investigator: Dr. Antonio Arrieta

Collaborators: Drs. Katrine Whiteson, David Michalik

Project Title: Addressing the Fear Factor in Neonatal Serious Bacterial Infections: Distinguishing E Coli From Bacteremia, Urinary Tract Infection, and Bacteremic Urinary Tract Infection in Infants <28 Days vs. >28 Days to 90 Days Old by Pairing E. Coli Genome Analysis with Clinical Data

 

Principal Investigator: Dr. Joanne Starr

Collaborators: Drs. Richard Gates, Sharief Taraman, Mary Zupanc, Paul Yost, Michele Domico, Juliette Hunt, Tammy Yoon, Kimberley Lakes

Project Title: Seizures and Neurodevelopmental Outcomes in Mild Hypothermic Cardiopulmonary Bypass

 

Principal Investigators: Dr. Sharief Taraman and Ruth McCarty

Collaborators: Drs. William Loudon, Frank Hsu

Project Title: The Use of Traditional Chinese Medicine (TCM) as a Complementary Treatment of Pediatric and Young Adults with Post-Concussive Syndrome

CHOC Stem Cell Production Facility to Accelerate Research into Rare Neurological Diseases

StemCellLabpicCHOC Children’s new stem cell production facility, slated to open late this summer, will allow CHOC researchers to produce patient-specific cells for immune-matching therapies that could positively impact fatal neurological diseases in children – all at a fraction of the cost of building a larger, more complex laboratory.

Within the state-the-art softwall clean room, CHOC researchers will study a stem cell-based therapy for the treatment for mucopolysaccharidosis (MPS-1), a rare and progressive neurodegenerative disease that typically claims patients before they reach the age of 10.

“Based on the results of animal trials we’ve conducted so far, we have a high degree of confidence that stem cell-based therapy will work to treat MPS-1,” said Philip Schwartz, Ph.D., senior scientist at the CHOC Children’s Research Institute and managing director of the National Human Neural Stem Cell Resource.

“If our research is successful, the approach could be used to treat a number of other immune-based diseases that damage the nervous system, like multiple sclerosis,” Dr. Schwartz said.

The approach involves using umbilical cord blood to replace a patient’s immune system, then implanting neural cells derived from the same blood into the brain to repair and prevent brain damage.

While implanting cells directly into the brain isn’t new, current treatment protocols require that patients take immunosuppressant drugs to reduce the risk of rejection, which leaves them vulnerable to a host of infections. Standard procedures for replacing the immune system, like bone marrow transplants, aren’t effective for patients with brain disorders caused by their underlying disease because the transplanted cells don’t cross the blood-brain barrier and therefore don’t slow the progression of brain disease.

The new facility will be one of less than a dozen in the nation and the only one that is focused on immune matching rather than immune suppression.

Dr. Schwartz estimated that it would require about five years of work to establish a program before approaching the U.S. Food and Drug Administration for approval to begin Phase I clinical trials. The current research project is supported by a $4.27 million grant from the California Institute for Regenerative Medicine.

Dr. Philip Schwartz Discusses Autism Research

Researchers are studying autism, a brain disease, by turning skin cells into brain cells through genetic manipulation, Philip Schwartz, Ph.D., a senior scientist at CHOC Children’s Research Institute, tells “American Health Journal.”

Scientists are using these cells with a goal to develop drug therapies for autism, as well as a diagnostic tool for the disorder, Dr. Schwartz says.

Learn more about autism research in “American Health Journal,” a television program that airs on PBS and other national network affiliates that reach more than 30 million households.

Each 30-minute episode features six segments with a diverse range of medical specialists discussing a full spectrum of health topics. For more information, visit www.discoverhealth.tv.

Philip Schwartz, Ph.D., is nationally recognized for his research in the stem cell field. His research focuses on the use of stem cells to understand the neurobiological causes of autism and other neurodevelopmental disorders. With funding support from CHOC, Dr. Schwartz established the National Human Neural Stem Cell Resource (NHNSCR) in 2001 to support national research in the field of neural stem cells by providing a reliable source for these cells to investigators nationwide

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