March 20, 2018

Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s, Howard Hughes Medical Institute investigator and professor at Baylor College of Medicine, has been awarded the sixth annual Ross Prize in Molecular Medicine by The Feinstein Institute for Medical Research at Northwell Health.

The Ross Prize is awarded annually by Molecular Medicine to scientists who have made a demonstrable impact in the understanding of human diseases pathogenesis and/or treatment, and who hold significant promise for making even greater contributions to the general field of molecular medicine.

“It is an honor to be recognized by Molecular Medicine and to join the prestigious roster of past Ross Prize recipients,” said Zoghbi, professor in the Departments of Pediatrics, Molecular and Human Genetics, Neurology and Neuroscience at Baylor. “I look forward to discussing my work and furthering a dialog that I hope will encourage young trainees to join the fields of neurobiology and molecular medicine.”

The prize, which includes a $50,000 award, will be presented to Zoghbi on June 5 at the New York Academy of Sciences in New York City, followed by lectures from Zoghbi and other eminent researchers. The Ross Prize is awarded through the Feinstein Institute’s peer-reviewed, open-access journal, Molecular Medicine, and made possible by the generosity of Feinstein Institute board members Robin and Jack Ross.

“Huda Zoghbi’s examination of the genetic causes for neurological diseases, such as spinocerebellar ataxia and Rett syndrome, has led to a better understanding of neurobiology,” said Feinstein Institute President and Chief Executive Officer Dr. Kevin J. Tracey, who also serves as editor emeritus of Molecular Medicine. “It is through her discoveries that researchers are able to identify new, potential therapies for these conditions that currently have no cure.”

Zoghbi’s research focuses on identifying the genetic causes of neurodegenerative and neurodevelopmental diseases and a broader understanding of neurobiology. Her lab, along with Harry Orr’s team at the University of Minnesota, discovered that excessive repeats of the DNA segment, CAG, in the ATAXIN-1 gene causes the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1). Over time, SCA1 may cause mental impairment, numbness, tingling or pain in the arms and legs and uncontrolled muscle tensing, wasting and twitches. Understanding the genetic cause for SCA1 has inspired additional research that may identify a therapeutic strategy for this condition that affects coordination and balance, difficulties with speech and swallowing, and weakeness in the muscles that control eye movement.

Zoghbi’s lab also has identified the genetic mutations that cause Rett syndrome. Rett syndrome mostly targets young girls and is a postnatal neurological disorder which causes problems in diverse brain functions ranging from cognitive, sensory, emotional, and motor to autonomic functions. These can affect learning, speech, sensations, mood, movement, breathing, cardiac function and even chewing, swallowing and digestion. Zoghbi’s discoveries provide a framework for understanding this disorder as well as the MECP2 duplication disorder and for charting a path for potential therapeutic interventions.

January 30, 2018

Dr. Huda Zoghbi was awarded the National Order of the Cedar, Knight grade by Lebanese President General Michel Aoun at a ceremony held in January at the Presidential Palace in Baabda.

Zoghbi is the founder and director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine, a Howard Hughes Medical Institute investigator, and holds the Ralph D. Feigin, MD, Endowed Chair in Pediatrics.

This prestigious honor touches close to home as Zoghbi was born and raised in Beruit, Lebanon’s capital and largest city. She received her Bachelor of Science degree from American University Beirut (AUB).

“It is an honor for AUB and indeed for Lebanon that the President of the Republic of Lebanon has conferred on Huda Zoghbi the Order of the Cedar,” said American University Beirut President Fadlo R. Khuri. “Thus, the greatest and most decorated scientist to have completed her undergraduate education at our university over the last several decades, a woman whose work is transforming the science and medicine of some of the world’s most serious neurological diseases, is now recognized by her native country’s highest award.”

Zoghbi’s hard work and dedication to the medical field spans through Texas Children’s and beyond. The National Order of the Cedar is a public service award and Lebanon’s highest honor.

“I am deeply honored and humbled to receive this great honor,” Zoghbi said. “I owe a lot of gratitude to my family who shaped me and to the institutions that educated me: Makassed and the American University of Beirut. I feel fortunate that I grew up and spent my formative years in Lebanon and I hope the culture that inspired me to seek knowledge will continue to inspire and empower the youth of Lebanon.”

August 22, 2017

When Bristol Dunlap was born, she was perfectly healthy. But by the time she was three months old, she was failing to reach her milestones and began showing worrisome symptoms.

“She could not lift her head up or sit upright, her body was unusually floppy, and her left eye began turning inward even though her vision was fine,” said her mother Evonia Dunlap. “As my daughter grew older, she was slow to crawl, stand and walk, and had difficulties in chewing, swallowing and talking.”

Bristol was diagnosed with congenital hypotonia which explained her poor muscle tone throughout her body. While therapy helped her daughter sit, walk and talk, there was one thing Dunlap wanted to know: What caused Bristol to develop hypotonia?

After seeing many specialists and undergoing a battery of diagnostic tests with still no answer, the family’s five-year medical odyssey ended at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s, where they were referred to neurologist Dr. Hsiao-Tuan Chao and Dr. Michael Wangler, geneticist and assistant professor of Human and Molecular Genetics at Baylor College of Medicine.

Through the NIH-funded Undiagnosed Disease Network (UDN), which brings together experts from across the country to help solve mysterious medical conditions by searching for their genetic basis, Chao and Wangler learned of a 7-year-old boy who exhibited symptoms similar to Bristol’s and also carried a point mutation in the Early B-Cell Factor 3 (EBF3) gene.

After re-examining Bristol’s exome sequencing results, they found she, too, carried the same mutation that produces a defective EBF3 protein. Since this protein is a master regulator of hundreds of other genes, even the tiniest alteration in its function could potentially cause widespread damage to the nervous system and muscles.

A referral center for undiagnosed diseases

Like the Dunlaps, many patient families are referred to Texas Children’s because of our renowned expertise and specialization in the diagnosis of diseases that are rarely seen and often unrecognized. Besides bringing together experts in genetics, pediatrics and neurology at Texas Children’s and its academic partner, Baylor College of Medicine, the UDN unites clinicians and scientists from across the country to help solve the most difficult medical cases. It is one of seven UDN sites nationwide.

More than 50 percent of UDN patients exhibit neurological symptoms. Texas Children’s chief of Neurology Dr. Gary Clark is one of the co-leaders of the UDN program at Texas Children’s and Baylor, and works closely with Texas Children’s neurologist Dr. Lisa Emrick in solving these mysterious neurological disorders.

“When a patient is referred to our UDN site, their DNA sample is submitted for sequencing,” said Emrick. “We conduct phenotyping and provide our UDN and NRI partners with the clinical patient data they need to help identify variant genes that may be responsible for a patient’s disease. Before advanced technologies like sequencing, only a small percent of these cases could be diagnosed.”

In addition to state-of-the-art medical imaging, metabolomics, and genetic testing including genome sequencing and exome sequencing, clinicians and researchers in the UDN rely on the Model Organism Screening Center (MOSC), where genes are studied in fruit flies to help diagnose patients. The center is led by Dr. Hugo Bellen, professor of Molecular and Human Genetics and Neuroscience at Baylor; Dr. Shinya Yamamoto, NRI investigator and assistant professor at Baylor; and Wangler. This dynamic team uses fruit flies, Drosophila melanogaster, to study new disease candidate genes and variants. They also closely collaborate with researchers at the University of Oregon in generating zebrafish models to study origins of disease.

In the MOSC, researchers combine bioinformatics analysis and experimentation in these ideal organism models to determine whether a specific variant identified in the genome of the patients may be responsible for the disease. “Integration of human genomics and experiments in simple model organisms such as fruit flies and zebrafish greatly facilitates disease diagnosis and mechanistic studies,” said Bellen.

“An exciting technique we developed is a way to humanize a fly gene,” said Yamamoto. “By knocking out the homologous gene in the fly and replacing it with the human gene, we can test the specific variant found in the patient to see how well it performs.”

Since fruit flies share many similar genes with humans, they have become a powerful model organism for the study of genetics. To study human disease in fruits flies, scientists mutate, or disrupt, the same gene that is known or suspected to cause the disease, and then figure out why mutations with this gene leads to disease.

Through collaboration with the UDN, Texas Children’s and Baylor continue to make significant strides in helping to accelerate the diagnoses of previously undiagnosed and rare neurological conditions.

For the Dunlap family, this provides a source of encouragement.

“While the journey to find a cure for our daughter’s illness has just begun, we are happy to finally have some answers,” Evonia said. “We are thankful for the pioneering work being done by physicians and researchers at Texas Children’s.”

July 17, 2017

Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Institute at Texas Children’s and professor in the departments of pediatrics, molecular and human genetics, neurology, and neuroscience at Baylor College of Medicine, received the 2017 Switzer Prize from the David Geffen School of Medicine at UCLA for excellence in biological and biomedical sciences research.

The Switzer Prize recognizes discoveries in basic research in the biological and biomedical sciences that have the potential to inspire transformative breakthroughs in medicine. It is awarded annually to an individual investigator whose recent work has revealed new paradigms, illuminated biological processes or pathways, or explained the origins of pathologies or diseases.

The David Geffen School of Medicine at UCLA established the prize to promote the importance of basic sciences research, which advances the understanding of biological systems and human physiology. Such research – a priority at UCLA – is essential to continued improvements in the diagnosis and treatment of a wide variety of illnesses.

The Switzer Prize is named in recognition of the generosity of Irma and Norman Switzer, who made a major gift to the David Geffen School of Medicine at UCLA.

Zoghbi’s research includes identifying a gene mutation that causes Rett syndrome, a severe genetic disorder that mostly affects girls. She will deliver the Switzer Prize lecture at UCLA in February 2018.

June 6, 2017

Dr. Benjamin Arenkiel, a researcher at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s has received a 2017 Michael E. DeBakey, M.D., Excellence in Research Award, a prestigious honor given annually to Baylor College of Medicine faculty who have made the most significant published scientific contribution to clinical or basic biomedical research during the past three years.

“Arenkiel is an extraordinarily gifted scientist who has made many exciting and notable discoveries in the area of neuroscience,” said Dr. Huda Zoghbi, director of the NRI who nominated Arenkiel for this prestigious award. “The papers he published in the last couple of years open up new exciting areas of research into sensory maps as well as the circuits of feeding behavior.”

Since joining the Baylor faculty, Arenkiel and his team have published and/or co-authored 32 manuscripts. In addition, the Arenkiel lab now focuses on three areas of science that each have resulted in publications in high-impact journals including Developmental Cell, Neuron, Nature, and Nature Neuroscience.

Arenkiel was presented with the DeBakey Excellence in Research Award on May 15. To learn more about the scientific research that garnered Arenkiel the DeBakey award, see below:

Nature Neuroscience: Using contemporary genetic approaches, the Arenkiel lab has recently described novel roles for neuropeptide signaling in synaptic remodeling within the adult nervous system. Synapse and circuit formation and function serves as a platform for their ongoing work. Arenkiel and his lab found that, in contrast to the refinement observed for excitatory maps, inhibitory sensory maps became broader with maturation. However, like excitatory maps, inhibitory sensory maps are sensitive to experience. These data describe the development of an inhibitory sensory map as a network, highlighting the differences from previously described excitatory maps.

Developmental Cell: In this paper, Arenkiel capitalizes on the olfactory system circuits system to understand how newly born neurons integrate into an existing network in the adult brain. Using the rodent olfactory system as a model, their work strives to understand how the circuits that comprise and modulate the olfactory bulb contribute to olfaction. This research shows that local corticotropin hormone signaling onto adult-born neurons promotes and/or stabilizes chemical synapses in the olfactory bulb, revealing a neuromodulatory mechanism for continued circuit plasticity, synapse formation and integration of new neurons in the adult brain.

Nature: Most recently, Arenkiel has initiated new and creative experiments to further probe neuronal synapse and circuit formation in the mouse brain. His lab has discovered a novel mechanism by which cholinergic signaling in the basal forebrain exerts a strong influence on body weight control. His group has serendipitously uncovered novel circuits that govern convergent hypothalamic circuits that influence feeding behavior, sensory processing and stress. He has since taken a keen interest in the feeding behavior circuits. This manuscript has been positively received by the scientific community as well as the pay press and was highlighted in the Wall Street Journal.

May 23, 2017

Drs. Hsiao-Tuan Chao and Laurie Robak, physician-scientists at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s, received scholarship grants from the American Academy of Neurology (AAN) to support studies on neurodevelopmental and neurodegenerative diseases.

Chao, a postdoctoral associate in the laboratory of Dr. Hugo J. Bellen was awarded the 2017 Neurology Research Training Scholarship for her proposed study titled, “Transcriptional Dysregulation of Neural Circuits in Neurodevelopmental Disorders.” Using the laboratory fruit fly and mouse, she will explore how changes in the function of master regulators of gene expression, like EBF3, can cause childhood neurologic diseases. Chao’s discoveries will provide some answers and improve the quality of life for many of these children and families.

Robak is a postdoctoral fellow in the laboratory of Dr. Joshua Shulman. She was awarded the 2017 Clinical Research Training Fellowship in Parkinson’s Disease for her proposal titled, “Elucidating Genetic Links Between Lysosomal Storage Disorders and Parkinson’s Disease.” Her study will identify lysosomal storage disorder genes as risk factors for Parkinson’s Disease, which will hopefully lead to improved diagnosis and risk assessment, and development of novel therapeutic strategies.

Twenty award winners, including Drs. Chao and Robak, were recognized at the 69th Annual Meeting of AAN, the world’s largest association of neurologists in April.

Click here for more information about their proposed research studies.

April 18, 2017

On April 10, more than 600 guests attended the Forum Luncheon at the Marriott Marquis in downtown Houston to meet internationally renowned neurogeneticist Dr. Huda Zoghbi and learn about the remarkable breakthroughs being made at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine.

President and CEO Mark A. Wallace delivered opening remarks including a video documenting the unfolding story of the NRI and how Texas Children’s bold vision of establishing the world’s first basic research institute dedicated to the study of childhood neurological diseases became reality as a result of the hospital’s incredible leadership which he describes as Texas Children’s “secret sauce.”

ABC 13 Anchor Melanie Lawson moderated the one-hour long Q-and-A discussion with Zoghbi, director of the NRI. In addition to learning about Zoghbi’s early career before making the transition to neuroscience research, Zoghbi shared her collaborative vision for the NRI and spotlighted some of the exciting new discoveries emerging from the numerous labs at the NRI.

“To understand a disease, you have to know the root cause,” Zoghbi said. “Once you know the root cause, you can then create an animal model of the disease, dive into the mechanism and find an entry to a therapeutic manipulation. Genetics is one way to find the root cause of disease.”

Since the NRI opened in 2010, Zoghbi highlighted several recent discoveries that have opened new doors for developing therapeutic targets for various neurological diseases:

  • Dr. Benjamin Arenkiel found a small group of cells in the basal forebrain play a major role in the control of appetite. In mouse studies, when these cells are manipulated a certain way, the animal either eats constantly and becomes obese or eats little and loses weight. Arenkiel’s discovery paves the way for developing new therapies to treat obesity and other eating disorders in children and adults.
  • In collaboration with Drs. Juan Botas and Zhandong Liu, NRI researchers have identified a potential new strategy to prevent Alzheimer’s disease. They found that an over accumulation of the protein tau can make the brain vulnerable to degeneration. By developing new drugs to keep tau at levels that are not toxic, this could either prevent or delay the development of Alzheimer’s and other degenerative diseases caused by toxic tau accumulation.
  • Drs. Andrea Ballabio and Marco Sardiello discovered the function of a gene called Transcription Factor EB that helps cells clear up accumulated proteins, which is important for nerve cells to survive. Based on this scientific breakthrough, new clinical trials are underway that will help slow down or stop the progression of disease in patients with Batten disease by improving the clearing function of the brain.
  • Drs. John Swann, Anne Anderson and their team found that there are many molecular and biochemical changes that drive the growth and over-activity of brain cells in epilepsy patients. They were able to define a way to treat these seizures based on biochemical studies in cancer, which has helped to eliminate uncontrollable seizures in children.
    The NRI Forum Luncheon also included inspirational stories from several patient families who were present at the event, and who have benefitted from the life-altering research emerging from the NRI to improve the outcomes and quality of life for patients with a myriad of neurological disorders.

Prior to this event, Texas Children’s Development also hosted a reception to unveil a photography exhibit by Karen Sachar honoring the special needs children in the Greater Houston community. The reception included a short presentation from NRI researcher Dr. Christian Schaaf.

Click here to watch the video of the entire Luncheon Forum program.

Click here to watch specific patient story videos that were featured at the event.