Dr. David Goldstein to direct Institute for Genomic Medicine at Columbia University

NEW YORK (September 23, 2014) — David Goldstein, PhD, will join Columbia University as professor of genetics and development in the College of Physicians and Surgeons and director of a new Institute for Genomic Medicine in partnership with NewYork-Presbyterian, effective January 1, 2015. Dr. Goldstein will be responsible for building a program that comprehensively integrates genetics and genomics into research, patient care, and education at Columbia University Medical Center (CUMC) and NewYork-Presbyterian and that develops programs to prepare students for careers in the expanding field of genomic and personalized medicine.

David Goldstein, PhD, will join Columbia University as professor of genetics and development and director of a new Institute of Genomic Medicine. (Image Credit: Duke Photography)

Dr. Goldstein’s role includes serving as an adviser to Columbia University President Lee C. Bollinger and Executive Vice President for Health and Biomedical Sciences Lee Goldman, MD, on the genetic and genomic components of Columbia’s university-wide initiative in precision or “personalized” medicine, which was announced in February.

“Having a pioneering researcher like David Goldstein join us marks a crucial next step in our initiative to be at the forefront of genomics, data science, and the core science and engineering disciplines essential to this emerging field of truly humanistic medicine,” said President Bollinger. “The potential for progress in this broad subject encompasses not only new cures for disease, but also virtually every part of the University, including areas that explore fundamental issues of human self-understanding, as well as the legal, policy, and economic implications of revolutionary changes in knowledge and practice.”

Dr. Goldstein’s research has focused on identifying the relationship between human genetic variations and diseases such as epilepsy, hepatitis C, and schizophrenia, as well as the response of these diseases to pharmacologic treatments. In addition to his leadership of the Institute for Genomic Medicine at CUMC, he will have a faculty appointment at the New York Genome Center, as well as one in neurology at Columbia’s College of Physicians and Surgeons.

“David Goldstein has shown himself to be both an innovative scientist and a visionary leader in genetic, genomic, and personalized medicine,” said Dr. Goldman, who is also the Harold and Margaret Hatch Professor of the University and dean of the Faculties of Health Sciences and Medicine at CUMC. “Working with our partners across Columbia and at New York-Presbyterian, Dr. Goldstein will help us establish a fully integrated genetics and genomics research environment to maximize the scientific possibilities and apply them to the frontiers of patient care and public health.”

“Personalized medicine and targeted therapies represent the future of patient-centered health care,” said Steven J. Corwin, MD, CEO, NewYork-Presbyterian. “Dr. Goldstein’s expertise in genetics will help us not only to tailor individualized treatments for patients, but  also to identify diseases before they develop. His work will have a transformative impact on patient care at NewYork-Presbyterian.”

Dr. Goldstein comes to Columbia from Duke University, where he has been director of the Center for Human Genome Variation and the Richard and Pat Johnson Distinguished University Professor, with appointments in the departments of molecular genetics & microbiology and biology. He joined Duke in 2005 after six years at University College London, which named him Honorary Professor in 2007. He received his PhD in biological sciences from Stanford University in 1994.

“The vision of Columbia University and NYP to create a truly integrated environment for research, clinical application, and student instruction is exactly the right vision,” said Dr. Goldstein. “Human genomics is creating breathtaking new opportunities to better understand the biology of disease and to provide more effective and more accurately targeted therapies. Capitalizing on these opportunities and ensuring that clinical applications adhere to the highest-possible scientific standards requires close collaborations among researchers, the clinical community, and patients and their families. I am thrilled to be joining Columbia University at this pivotal time in my field, and I am honored to participate in Columbia’s university-wide initiative in precision medicine.”

Dr. Goldstein was elected a fellow of the American Association for the Advancement of Science in 2013 and received one of the first seven nationally awarded Royal Society/Wolfson research merit awards in the United Kingdom for his work in human population genetics. Also in 2013, Dr. Goldstein chaired the Gordon Research Conference in Human Genetics. He serves on the Advisory Council at NIH’s National Institute of Neurological Disorders and Stroke.

The task force President Bollinger announced in February is co-chaired by Dr. Goldman and Columbia Provost John Coatsworth, PhD.

About:

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

NewYork-Presbyterian Hospital/Columbia University Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and its academic partner, Columbia University College of Physicians and Surgeons. NewYork-Presbyterian/Columbia provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian/Morgan Stanley Children’s Hospital, NewYork-Presbyterian Hospital/Westchester Division, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian/Lower Manhattan Hospital. The hospital is also closely affiliated with NewYork-Presbyterian/Lawrence Hospital in Bronxville. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area, according to U.S. News & World Report, and consistently named to the magazine’s Honor Roll of best hospitals in the nation. For more information, visit www.nyp.org.

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NGLY1 Profile: Grace, age 4

Patient: Grace, age 4
Parents: Kristen and Matt
Sibling(s): none

History

Grace was delivered via emergency Caesarean section at Lucile Packard Children’s Hospital at Stanford in 2009. The doctors hit the “crash” button because of decreasing fetal heart rate. Grace's Apgars were 4 at 1 minute and 8 at 5 minutes. She spent the first 2 nights in our room at the hospital, but she was extremely lethargic, was not eating, or going to the bathroom. Her eyes looked hazy and quite gray. Her pediatrician ran a series of blood tests and Grace's CRP (a non-specific marker for stress such as an infection) was extremely elevated (~12). The doctors quickly moved Grace to the NICU for a little over 2 weeks.

The doctors ran all kinds of tests on her from a spinal tap to a brain ultrasound to an EKG to multiple stomach x-rays. They never could tell if she had a viral or bacterial infection, but they were fairly sure it was one or the other. Consequently they gave her 2 full weeks of antibiotics and a few days of antivirals. Every 24 to 48 hours Grace improved slightly. It seemed the drugs were working. Toward the end of her 2-week stay, her liver enzymes (known as LFTs for short) were shown to be elevated and her platelet count was dangerously low. The doctors thought this was most likely a residual effect of the infection and sent us home to be monitored as an outpatient (we were told there was nothing more they could do in the intensive care unit). Shortly before Thanksgiving 2009, the liver enzymes normalized and an abdominal ultrasound showed the liver working normally. We felt like we dodged a bullet and we decided to retest at 5 to 6 months of age after working closely with Grace's gastroenterologist at Stanford.

Unfortunately the tests at 5 months showed elevated AST and ALT (GGT was normal). On top of the elevated LFTs, Grace was falling behind developmentally. This is where we mobilized in a big way because clearly this was not a reaction to an infection and was not isolated to GI. This was something very serious and something genetic.

We assembled the best and brightest clinical minds in several disciplines at many world-class centers. We made 3 trips to Columbia, 2 trips to CHOP, 2 trips to NIH, 2 trips to Baylor College of Medicine / Texas Children’s Hospital, 1 trip to University of Colorado, Boulder, 1 trip to John Hopkins, and countless trips to Stanford and UCSF. From the age of 6 months to 3 and ½ years old, we pursued a primary mitochondrial disease.

Whole Genome Breakthrough

After exhausting all of our testing options, two centers (Stanford and Baylor) independently performed whole genome sequencing (WGS). We wanted to see if both came up with the same conclusion independently. Stanford and Baylor came back with the exact same leading gene candidate (SUPV3L1). This gene fit Grace’s phenotype and the theory that Grace’s condition was mitochondrial. We spent nearly 1 year investigating this gene under the close supervision of Dr. Greg Enns at Stanford and Dr. Vamsi Mootha at Harvard / Broad. Unfortunately the functional assays did not prove anything.

In addition to SUPV3L1, Stanford and Baylor flagged several other “candidates” (genes that looked suspicious). We explored several of these, but not all. In February 2013, Kristen, Grace, and I flew back down to Houston for 4 days. Under the guidance of Dr. Huda Zoghbi, we met with over 15 doctors in 3 days. Two of the doctors we met with were Richard Gibbs and Matthew Bainbridge. We asked them to re-run our data. Within a few days of meeting, Matthew emailed asking if Grace produced tears. We had noted to several specialists that Grace did not produce streaming tears when sad or hurt, but this clue didn’t help us over the previous years. Richard and Matthew had flagged one gene in particular (NGLY1). This gene was actually flagged by Stanford back in 2011, but it was a mystery gene. At the time, no databases or medical literature showed one human being having a NGLY1 mutation. Unbeknownst to Stanford and us, the doctors at Duke had diagnosed Bertrand and were preparing to publish. Once they did publish, Richard and Matthew found it. The phenotypes, while not perfect matches, were close. The lack of tears while crying was a significant clue in piecing the puzzle together.

Current Health Condition

Grace is stable. While she has many challenges, she is amazingly happy and resilient. Despite spending a lot of time in hospitals and clinics, she is relatively healthy for a 4 year old NGLY1 patient. Colds affect her more than most kids (her body gets “floppy”), but she recovers quickly. Developmentally she is more like a 12 to 18 month old. She can sit-up, pull-up to stand, “cruise” along furniture, and walk for short distance after pulling up to stand. She cannot talk. She has a few sounds and word approximations. She cannot point and has no pincer grasp (index finger + thumb). Her disease affects her central nervous system (CNS), liver, and muscle predominantly. She has microcephaly (small head), difficulty gaining and maintaining weight, alacrima (dry eyes), sleep apnea, and strabismus (eyes wander). The systems we have to keep close tabs of are liver, eyes, and lungs. The latter has showed some signs of aspiration, which is quite dangerous (pneumonia can be lethal in young kids with chronic / rare illness). Grace loves Elmo, books, music (Katy Perry, Taylor Swift, & Super Simple Songs), Super Grover 2.0, swimming, and horses.

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NGLY1 Profile: Mason, age 5

Patient: Mason, age 5

Parents: Sara and Mark

Sibling(s): none

Mason is five years old and was born at 34 weeks via emergency C-section because of bradycardia episodes, he was measuring small and my fluid level was dangerously low. He was a relatively 'normal' preemie, staying in the NICU for 24 days, his main issues were jaundice, finally passing the merconium, and learning to eat and hold his temperature. He was on oxygen for only the first 24 hours and progressed somewhat normally in the NICU. He had a Hirschprung's test done because it took him longer than 7 days to pass the merconium; but that test came back negative.



Mason came home weighing 5lbs, he cried almost all the time when he was awake, wouldn't sleep for longer than 45 mins at a time and projective vomited almost everything he ate. He was never very good at latching on, so I pumped for 3 months and bottle fed him, until putting him on specialty formula, all of which didn't help. He was tested for allergies and other than having a sensitive to dairy, there was nothing.

Mason never reached any developmental milestones and it wasn't until he was evaluated by Easter Seals and recommended to a neurologist that we knew something was very wrong. The neurologist suspected seizures from the very beginning, noticing his quick eye movements (I honestly didn't believe him because I never saw them). He also never stop moving - ever. It was like he was constantly twitching, but never the same motions over and over, just like his body couldn't ever relax. He was put on Keppra, and obviously because I didn't see the seizures in the first place, I never saw an improvement.

Mason was always a heavy breather, in fact we would joke that he was like Darth Vader. He went in for an MRI after the neurology visit and they refused to put him under because of the stridor. He saw an ENT who thought he just needed to grow a little bigger and hopefully his airway became strong; they attributed the stridor to the reflux. He finally got an MRI, and overall his brain was 'smaller' than normal, but there was nothing significantly glaring - little did I know this meant absolutely nothing!

At about 13 months, he was hospitalized for severe breathing issues; he sounded like he was breathing from a straw. It was at this 5 day stay where they did the muscle biopsy, found that he has only one kidney, and still attributed the stridor to severe reflux; they put him on feeding through an NG tube and his breathing seemed to get better so they sent us home. (Not to mention that they stuck him one million times trying to get an IV so they could fly him, then another million times to do tons of tests...he's one of the toughest little guys ever). They sent us home on a steroid, once he was off the steroid, the breathing got worse, so he was sent back to the hospital to get the Nissen Fundoplication surgery. The hope was that if he physically couldn't throw up, his airway wouldn't be burned by the acid and then his airway wouldn't be inflamed and breathing would improve. During the Nissen, they did a livery biopsy to check to Mito disease. It was after the muscle and liver they told us he had mito - I never realized that when they classified him with this it was because he had too much mitochondria!

Unfortunately, after another round of steroids and being sent home, his breathing was still awful, so they told us he would need to be trached. One month later, he had his trach surgery. We were told he would be kept asleep for a week so that he could heal and wouldn't pull at his trach - they kept him under for only a few hours after surgery and when he woke it was one of the most heartbreaking moments a mother could have, as I'm sure you can relate. For the first two months, we couldn't leave the floor, it was like the best moment of my life when we were allowed to walk around the entire hospital. In total, we were in the hospital from August to December. As difficult as it has been to get used to the trach, it has allowed him freedoms he never before had now that he can breathe.

Over a year ago we noticed his head drops and eye rolls getting significantly worse, mind you we took him off the Keppra, but thought we were ok because we never could see the seizure. Within 10 mins of his EEG, the on-call neurologist was called and Mason is literally having thousands of seizures a day; most go without anyone noticing, but they definitely get in the way of his development.

Mason cannot walk, he cannot talk, there is a 'light' on, he recognizes people and places, knows what he wants and can communicate without words and he smiles like it's Christmas watching Mickey Mouse. He can crawl and sit on his own and pull to stand. Overall he is the most incredibly loving and strong little boy.

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US Congress hears about NGLY1

On Tuesday, July 22, 2014, at 3:00 p.m. in 2322 Rayburn House Office Building, the Subcommittee on Health held a hearing entitled “21st Century Cures: Examining Barriers to Ongoing Evidence Development and Communication.” This hearing focused on issues surrounding continued evidence development and communication of information regarding treatments and cures in the real world setting.

In her opening statement, Rep. Diana DeGette (Colorado) used NGLY1 as an illustration, and goes on to ask, "What can we do to harness this [patient involvement and technology] in a much more systemic way, so that these types of communications can happen effortlessly both in the United States and with our colleagues around the world?"

Video automatically starts at Rep. DeGette's statements about NGLY1.

Learning about the benefits and risks of a drug or device does not end when the Food and Drug Administration approves, licenses, or clears the product for use in certain patients based on the evidence presented during the premarket review process. In many ways, the process is just beginning. 

Different uses for drugs and devices are being discovered constantly, many times for treatment of new conditions and diseases or for populations of patients other than for which they were initially approved. Treatment in the real world setting also provides the opportunity to learn more about both the benefits and risk profile of a drug and device for its indicated use, as well as other uses. 

Learning and data sharing regarding safety and efficacy are happening through a multitude of platforms around the globe. Dialogue regarding this enhanced learning--whether through the Internet, social networks, or other platforms--should be facilitated among doctors, patients, researchers, and scientists because the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients could help advance the discovery, development and delivery cycle.

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Boston Public Radio covers NGLY1

Boston Public Radio 07/21/2014

The segment on NGLY1 starts at 1:36:39.

Seth Mnookin, a professor in the MIT graduate program in science writing, talked about his new piece in The New Yorker titled "One of a kind: What do you do if your child has a condition that is new to science?"

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Benefit for Jordan & Jessie

The following is a fundraiser to improve the quality of life for one of our beautiful NGLY1 families by helping them purchase a handicap accessible van capable of transporting both of their daughters.

If anyone is interested in simply donating directly to this family, please let us know.  Thank you!

Everyday life for The Stinchcomb's is tough. Both girls who suffer from NGLY1 do not speak, they can not walk, they wear diapers, drink formula, use wheelchairs, and need constant attention. Tony and Pam provide all of this to their girls WITHOUT ANY OUTSIDE HELP. They see that the girls' needs are met to the best of their ability. Traveling, even to the grocery store, is nearly impossible, even with their Suburban. The one single thing that could change the quality of life for this family would be handicap accessible transportation. That is our goal with this fundraiser. Helping them achieve mobility so their family can function more like an every day family!  

This family is near and dear to our hearts so I wanted to do something special for them. You can help by placing an order online anytime between now and August 15th and I will donate 25% to the Stinchcomb Family! This is a great opportunity to help this sweet family, and also get a gift for someone special (or yourself)! Don't forget Christmas, Birthdays, Teachers and special occasions! 

Order at: 
http://www.heatherm.origamiowl.com/parties/StinchcombFundraiser405289/collections.ashx

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"Integrating Glycoscience"

This upcoming November 2014 at the annual joint meeting for the Society of Glycobiology and the Japanese Society for Carbohydrate Research, there will be an entire session dedicated to NGLY1!

The theme for the conference is "Integrating Glycoscience From Biology and Chemistry to Medicine".

NGLY1 session presenters will include researchers Tadashi Suzuki, Hudson Freeze, Hamed Jafar-Nejad, as well as two NGLY1 parents!  The Super Matts: Matthew Might and Matt Wilsey.

The NGLY1 session starts at 2:45pm on Tuesday, November 18th.  These talks are sure to be thought-provoking and inspiring.

If you'll be in Honolulu, Hawaii, don't miss it!

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