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Our Inspiration for Advancing Medicine The Patient as Muse baylor college of medicine quarterly review 2012 www.bcm.edu
Our Inspiration for Advancing Medicine
The Patient as Muse
baylor college of medicine quarterly review 2012
www.bcm.edu
THE TEXAS MEDICAL CENTER
BCM BITES
One of the great strengths of BCM is its location. BCM is in the heart of the Texas Medical Center, the largest health center in the world. This density of healthcare and research institutions provides fertile ground for collaborations on a scale not feasible elsewhere.
*Student numbers only include those of programs of health related member institutions. **Includes data from 9 academic member institutions.
Note: Shortly after the National School of Tropical Medicine at BCM joined the TMC another institution joined and additional institutions are frequently added. Therefore, numbers specified here change frequently.
The National School of Tropical Medicine at BCM, recently become the 51st member the Texas Medical Center.
TMC BY THE NUMBERS
TOTAL BUDGET
(All Institutions)
MEMBER INSTITUTIONS
– 26 agencies of government
– 25 private not-for-profit health-related institutions
TOTAL HOSPITAL BEDS
TOTAL SIZE (ALL CAMPUSES)
and Buildings
Annual Patient Visits
Annual InternationalPatient Visits
Employees
Full-time Students
Residents and Fellows
Visiting Scientists, Researchersand Students
1
(Top) The Lee and Joe Jamail Specialty Care Center.(Bottom) The second building on the McNair Campus was constructed to allow for flexibility. Portions of the interior are currently being developed to support a new model of care that is both patient-focused and efficient.
OUTPATIENT CENTER NAMED IN HONOR OF LEE AND JOE JAMAIL
Baylor College of Medicine’s outpatient clinic on the McNair Campus has been named the Lee and Joe Jamail Specialty Care Center in honor of the renowned Houston attorney and his late wife.
“Baylor College of Medicine has played a very important role in the history of our city and nation,” said Jamail. “Its achievements in training the finest physicians and in research and creative treatment are unsurpassed. Lee and I have always been proud of Baylor College of Medicine. It holds a very special place in our lives. I consider it a great honor and privilege to be recognized by such a quality, world renowned organization and know Lee would feel the same.”
The Jamail Specialty Care Center is the first completed building on BCM’s McNair Campus. Work is currently underway on a second building at this site. The outside hull of the building has been completed and the interior is designed to be flexible, allowing BCM to create patient-centered clinical care space as well as education and research spaces that will be able to meet the needs of the College, the Houston community and the U.S. healthcare system as these needs evolve over time.
BCM AFFILIATE—THE MENNINGER CLINIC—OPENS NEW CAMPUS
The Menninger Clinic celebrated its relocation to a new, 50-acre campus near the Texas Medical Center with a grand opening ceremony in April. The Menninger clinic moved to Houston from Topeka, Kansas, in 2003 as part of its relationship with Baylor College of Medicine and The Methodist Hospital.
During the opening festivities, Dr. Paul Klotman, president and CEO of BCM, said that the partnership between BCM and the Menninger Clinic is poised to transform psychiatry. He praised the hard work and commitment of Dr. Stuart Yudofsky, professor and chair of the Menninger Department of Psychiatry and Behavioral Sciences at BCM.
MOLECULAR AND HUMAN GENETICS CELEBRATES 25
The Department of Molecular and Human Genetics at Baylor College of Medicine recently celebrated its 25th anniversary. The Department has helped to shape and advance the study of genetics
throughout the genetic revolution of the past quarter century.
The Department, which is ranked number one in the country in funding from National Institutes of Health, is home to three members of the National Academy of Sciences, five members of the Institute of Medicine and three Howard Hughes Medical Institute Investigators.
As part of the celebration of this mile-stone, a video tracing the history of this Department and its numerous con tribu-tions to our understanding of health and disease was produced. To view the video, Tracking the Future through the Double Helix, visit www.bcm.edu/genetics/ history.cfm.
There is a seemingly limitless supply of healthcare needs in this country and around the world. Almost everyday, I hear of new approaches that BCM faculty and staff are developing to meet these needs.
In this issue of the BCM Quarterly we highlight some of these new initiatives. To fulfill growing demand for trained pro fessionals, our School of Allied Health Sciences has devel oped a Master’s in Orthotics and Prosthetics program (page 2). To provide new tools for researchers new companies are being launched with BCM developed technologies (page 8).
To meet the changing health care needs of our community and our nation, we are developing the McNair campus. The first step in this endeavor was the newly named Jamail Specialty Care Center (page 1). Soon this campus will be expanded with a second building, which is being developed with a unique approach to serve as a new model for healthcare delivery. I look forward to telling you more about our plans for the new McNair campus in future issues.
But, among all the newness, old values persist. The feature article in this issue focuses on a fundamental truth for physicians dating back to the most distant roots of our profession; in all we do—in the clinic, in the classroom, in the laboratory and in the community—our inspiration remains our patients. They are the driving force that pushes us to do more, to do better and to succeed.
Best regards.Paul Klotman, MD President and CEO, Baylor College of Medicine
Welcome toBCM Quarterly.
TABLE OF CONTENTS
BCM Update ...................................................... 1
Accolades ............................................................3
The Patient as Muse .........................................4
From Bench to Market.....................................8
Research Briefs ...............................................10
THE TEXAS MEDICAL CENTER
BCM BITES
One of the great strengths of BCM is its location. BCM is in the heart of the Texas Medical Center, the largest health center in the world. This density of healthcare and research institutions provides fertile ground for collaborations on a scale not feasible elsewhere.
*Student numbers only include those of programs of health related member institutions. **Includes data from 9 academic member institutions.
Note: Shortly after the National School of Tropical Medicine at BCM joined the TMC another institution joined and additional institutions are frequently added. Therefore, numbers specified here change frequently.
The National School of Tropical Medicine at BCM, recently become the 51st member the Texas Medical Center.
TMC BY THE NUMBERS
TOTAL BUDGET
(All Institutions)
MEMBER INSTITUTIONS
– 26 agencies of government
– 25 private not-for-profit health-related institutions
TOTAL HOSPITAL BEDS
TOTAL SIZE (ALL CAMPUSES)
and Buildings
Annual Patient Visits
Annual InternationalPatient Visits
Employees
Full-time Students
Residents and Fellows
Visiting Scientists, Researchersand Students
Baylor College of Medicine is the academic center around which the Texas Medical Center, the world’s largest health center, evolved.Within the four schools that compose BCM, our faculty creates, implements and shares new knowledge, systems and technologies that improve the lives of our neighbors, our nation and our world.
Baylor College of Medicine – Consistently ranked as one of the leading research-intensive medical schools by U.S. News & World Report and ranked fourth in the nation by StudentDoc.com, BCM is the least expensive private medical school in the U.S.
BCM Graduate School of Biomedical Sciences – BCM’s extensive research portfolio combined with faculty who are world-leaders in their field support 14 programs which are ranked among the top 10 percent of graduate programs in biological sciences.
BCM School of Allied Health Sciences – Drawing highly regarded applicants from throughout the region and the nation, the programs of BCM School of Allied Health Sciences consistently rank among the best in the country.
BCM National School of Tropical Medicine – This newest academic component builds on the College’s over 100-year legacy of caring for our local and global community. It is the only school in the nation dedicated to patient care, research and education related to neglected tropical diseases, the most common infections of the world’s poorest people.
BCM physicians provide state-of-the-art care to patients from Houston and around the world at the Baylor Clinic and our eight affiliated teaching hospitals.
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(Top) The Lee and Joe Jamail Specialty Care Center.(Bottom) The second building on the McNair Campus was constructed to allow for flexibility. Portions of the interior are currently being developed to support a new model of care that is both patient-focused and efficient.
OUTPATIENT CENTER NAMED IN HONOR OF LEE AND JOE JAMAIL
Baylor College of Medicine’s outpatient clinic on the McNair Campus has been named the Lee and Joe Jamail Specialty Care Center in honor of the renowned Houston attorney and his late wife.
“Baylor College of Medicine has played a very important role in the history of our city and nation,” said Jamail. “Its achievements in training the finest physicians and in research and creative treatment are unsurpassed. Lee and I have always been proud of Baylor College of Medicine. It holds a very special place in our lives. I consider it a great honor and privilege to be recognized by such a quality, world renowned organization and know Lee would feel the same.”
The Jamail Specialty Care Center is the first completed building on BCM’s McNair Campus. Work is currently underway on a second building at this site. The outside hull of the building has been completed and the interior is designed to be flexible, allowing BCM to create patient-centered clinical care space as well as education and research spaces that will be able to meet the needs of the College, the Houston community and the U.S. healthcare system as these needs evolve over time.
BCM AFFILIATE—THE MENNINGER CLINIC—OPENS NEW CAMPUS
The Menninger Clinic celebrated its relocation to a new, 50-acre campus near the Texas Medical Center with a grand opening ceremony in April. The Menninger clinic moved to Houston from Topeka, Kansas, in 2003 as part of its relationship with Baylor College of Medicine and The Methodist Hospital.
During the opening festivities, Dr. Paul Klotman, president and CEO of BCM, said that the partnership between BCM and the Menninger Clinic is poised to transform psychiatry. He praised the hard work and commitment of Dr. Stuart Yudofsky, professor and chair of the Menninger Department of Psychiatry and Behavioral Sciences at BCM.
MOLECULAR AND HUMAN GENETICS CELEBRATES 25
The Department of Molecular and Human Genetics at Baylor College of Medicine recently celebrated its 25th anniversary. The Department has helped to shape and advance the study of genetics
throughout the genetic revolution of the past quarter century.
The Department, which is ranked number one in the country in funding from National Institutes of Health, is home to three members of the National Academy of Sciences, five members of the Institute of Medicine and three Howard Hughes Medical Institute Investigators.
As part of the celebration of this mile-stone, a video tracing the history of this Department and its numerous con tribu-tions to our understanding of health and disease was produced. To view the video, Tracking the Future through the Double Helix, visit www.bcm.edu/genetics/ history.cfm.
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During tours of the DeBakey Museum over Alumni Weekend. Many alumni paused to admire a newly donated ancient anatomy text. Dr. Paxton Howard, BCM class of 1962 is pictured here during one such tour.
De humani corporis fabrica
Alumni are frequently encouraged to give to their alma mater. BCM alumnus, Dr. O. Howard “Bud” Frazier and his wife Rachel found a particularly unique way to give. On April 20, during Alumni Weekend, Frazier donated De humani corporis fabrica (On the Structure of the Human Body), an anatomy text dating back to the 1500s, to the DeBakey Museum and Library at BCM.
Authored by Flemish anatomist and physician Andreas Vesalius (1514-1564), the book was first published in 1543. “It was really the first attempt to scientifically describe the human body. Literally, Vesalius became the father of modern anatomy,” said Dr. William T. Butler, chancellor emeritus at BCM.
The book donated by Frazier, a 1967 alumnus of BCM and professor of surgery at BCM, is a second edition published in 1555. It includes important revisions, such as the description of the vein valves that remained undiscovered until 1546 when they were described to Vesalius by Italian physician Gianbattista Canano.
All this means that there is tremendous need for trained professionals to help individuals who have lost a limb or are in need of orthotic management. In keeping with Baylor College of Medicine’s mission to improve lives for the people of Texas, the U.S. and the world, BCM has made a commitment to help fill this need by creating a Master of Science in Orthotics and Prosthetics (MSOP) Program.
Only the seventh master’s degree program in the country, it is unique in that it is the only one to integrate a series of full time clinical rotations designed to meet the requirements of the National Commission on Orthotic and Prosthetic Education approved residency. Graduates of the program will be eligible to sit for board exams sponsored by the American Board for Certification in Orthotics, Prosthetics and Pedorthics.
Jared Howell has been named the director of the program, which will enroll its first group of students in July 2013.
FIRST SPACE MEDICINE TRACK FOR MEDICAL STUDENTS
Medical students who have an interest in space medicine can now take courses in the world’s first officially recognized space medicine track as they pursue their medical degree.
“This elective program through the Center for Space Medicine gives future physicians knowledge about physiological, psychological and medical issues associated with space exploration and the practice of medicine in harsh, remote environments,” said Dr. Jeffrey P. Sutton, director of the center. “The track is very popular among the students, and we are fortunate to have exceptional instructors, including physician-astronauts, flight surgeons and leading scientists from around the country.”
BCM TO OFFER MASTER OF SCIENCE IN ORTHOTICS & PROSTHETICS DEGREE
There are 1.7 million persons with amputation in the U.S. Global estimates are harder to pinpoint, but it is likely that there are between 12-20 million persons with amputation. More than 20 million people in the U.S. need orthotic management for physical disability or injury. Globally the need for orthotic management may be hundreds of millions.
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The American Society of Nephrology launched a new scholars program named after Dr. William E. Mitch, director, section of nephrology section and professor of medicine at BCM.
Dr. Kalpana Kannan, a postdoctoral associate in pathology and immunology at BCM, received a 2012 Prostate Cancer Foundation Young Investigator Award.
Dr. Kalpalatha Guntupalli, professor and chief of pulmonary, critical care and sleep medicine in the Department of Medicine at BCM, recently received the Pravasi Bharatiya Samman Award from the Indian government.
Dr. Thomas Wheeler, professor and chair of pathology and immunology at BCM, received the Harlan Spjut Award from the Houston Society of Clinical Pathologists. The award is named for Dr. Harlan Spjut, who was a faculty member of the Department of Pathology at BCM.
Dr. Malcolm Brenner and his colleagues have been recognized by the Clinical Research Forum
“Dr. Dora Angelaki, professor and chair of the department of neuroscience at BCM, has been awarded the inaugural Pradel Research Award in Neuroscience by the National Academy of Sciences. The award was given to Angelaki in recognition of her work, which has clarified how vestibular and visual signals combine to mediate perception and to direct appropriate motor behaviors.”
Dr. Paul Klotman, president and CEO
ACCOLADES
for having one of the top 10 clinical research accomplishments published in the last two years. Their work, which was published in the New England Journal of Medicine, identified a new approach to make stem cell transplantation safer.
Dr. Christie Ballantyne, professor of medicine and section chief of cardiology and cardio vascular research in the Department of Medicine at BCM, was awarded the Louis M. Sherwood Award by the Association of Clinical Research Professionals.
Medscape named an article by Dr. Neena Abraham, associate professor of medicine – gastroenterology at BCM, the most read article of 2011 by gastroenterologists.
Dr. Michael H. Heggeness, professor of orthopedic surgery at BCM, was named president of the North American Spine Society.
Anita Rao, a local high school student who was mentored by leaders at the BCM Sleep Center, was named as the first and only ambassador for the Alliance for a Healthier Generation.
Dr. Ashley Clinton, assistant professor in the Menninger Department of Psychiatry and Behavioral Sciences at BCM, was honored by the Veterans County Service Officers Association of Texas (Harris County) for her work with veterans who served in Iraq and Afghanistan.
Dr. David Nelson, the Cullen Foundation Chair in Molecular and Human Genetics at BCM, was appointed editor of the American Journal of Human Genetics.
Dr. David Eagleman, assistant professor of neuroscience at BCM, was named one of the Brainiest and Brightest Idea Guys for 2012 by Italy’s Style Magazine.
Dr. Robert Todd, chair of medicine at BCM, was elected as a board member at large to the Association of Professors of Medicine.
Dr. Peggy Smith, professor of obstetrics and gynecology at BCM and director of the Baylor Teen Health Clinic, was selected as a 2012 Our Choice Honoree by the Missouri City Chapter of The Links Inc.
Dr. Benjamin Archer, professor of radiology at BCM, was elected Distinguished Emeritus Member of the National Council on Radiation Protection and Measurements.
Dr. Blase Carabello, professor of medicine – cardiology at BCM and chief of medicine at the DeBakey VA Medical Center, received the Simon Dack Award for Outstanding Scholarship from the editors of the Journal of the American College of Cardiology.
Dr. Tyson Pillow, assistant professor of medicine – emergency medicine at BCM, received the 2012 Council of Emergency Medicine Residency Directors Faculty Teaching Award.
Dr. Hashem El-Serag, the Dan L. Duncan Professor of Medi cine and chief of gastro enterology and hepatology in the Department of Medicine at BCM, has been selected to lead the journal, Clinical Gastroenterology and Hepatology.
Dr. Angshumoy Roy, molecular genetic pathology fellow at BCM, was awarded the 2012 Young Investigator Award by the Society for Pediatric Pathology.
Dr. David Berger, professor of surgery at BCM and executive of the Operative Care Line at the Michael E. DeBakey VA Medical Center, was elected president of the Association of VA Surgeons.
Dr. Margaret Ann Goldstein, professor emeritus of medicine in the section of cardiovascular research at BCM, was elected as a Fellow to the Microscopy Society of America.
Dr. Douglas D. Koch, professor and the Allen, Mosbacher, and Law Chair of Ophthalmology at BCM, received the Innovator’s Medal from the American Society of Cataract and Refractive Surgery.
Gorman Preston, a student in BCM’s physician assistant pro gram, received a Memorial Hermann Volunteer Service Scholarship.
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Top left: Dr. Brendan Lee was inspired by Jonathan Oliphant to find answers that would help him lead a longer, richer life.
Top right, center left and bottom left: Jonathan Oliphant with his family.
Bottom right: A proposed model for the nitric oxide synthase complex. ASS: Argininosuccinate synthetase; ASL: Argininosuccinate lyase; NOS: nitric oxide synthase; HSP90 Heat shock protein 90; CAT1: Cationic amino acid transporter (Arginine transporter).
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In the spring of 2010, Jamie Oliphint was desperate. Her son Jonathan’s blood pressure was out of control and none of the usual medications could bring it down. The high blood pressure had caused Jonathan’s heart to enlarge, impeding its ability to pump blood.
High blood pressure is never normal in a youngster, and in Jonathan’s case, it was especially dangerous. Mrs. Oliphint turned to the physician who had been treating and doing research on Jonathan’s genetic disorders since the youth was a youngster.
Dr. Brendan Lee received her desperate email, and finally, he thought he might have an answer. It was near the end of a long quest that Lee, professor of molecular and human genetics at BCM, began when he first saw Jonathan as a young child in the metabolic clinic at Texas Children’s Hospital. The problem led Lee back to the laboratory for years of painstaking experiments.
Two years ago, he was finally able to bring the results back to the youngster’s bedside for a successful treatment. He and his colleagues Drs. Sandesh Sreenath Nagamani and Ayelet Erez, both assistant professors of molecular and human genetics at BCM, described the treatment in the American Journal of Human Genetics.
“Having an immediate impact on the life of a child is the most rewarding feeling,” said Lee. “The theme we have pursued in the study of these rare genetic diseases is that they can lead to insights into more common disease mechanisms, and this has borne true. We cannot, however, forget the direct and immediate impact our work can have on the patients with the rare diseases. This is a beautiful example of that.”
The problem was that Jonathan’s genetic disorder—argininosuccinic aciduria—meant that he lacked a functional gene to make an enzyme called argininosuccinate lyase.
The Patient: The Muse Poets have Calliope. Astronomers have Urania. Musicians have Euterpe.
And physician-scientists have their patients. Inspired by the plights of the
patients they encounter in clinic, Baylor College of Medicine researchers
head to the laboratory and, in many cases, find solutions that help not only
the individual or those with a specific disease, but also have far reaching
implications for healthcare and science.
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Jonathan’s mother also said that after the treatment Jonathan showed some improve-ment in testing and he seemed more aware of the world around him.
Lee wants still more information before the treatment is used more widely, and he is planning a clinical trial of the treatment in children with Jonathan’s disorder.
NEW DIRECTIONS IN AUTISM RESEARCH INSPIRED BY A PATIENT
As a resident Dr. Huda Zoghbi met a patient who changed the course of her life. The girl had been a perfectly healthy child, playing and singing and otherwise acting like a typical toddler. Around the age of two, she stopped making eye contact, shied away from social interactions, ceased to communicate, and started obsessively wringing her hands. “She made a huge impression on me,” says Zoghbi, who set out to determine what could have caused this sudden neurological deterioration.
Sixteen years after she saw that first patient, Zoghbi and her collaborators identified MECP2, the gene responsible for Rett syndrome. But the path to treatments, even for the symptoms of the disease, has been long and rocky.
Rett shares common elements with a number of disorders including Angelman, fragile X syndromes and tuberous sclerosis disorder. All produce autism spectrum symptoms and all have as their underlying cause a synaptic dysfunction (a malfunctioning at the juncture where neurons communicate).
Decades of research have led to new understandings of diseases like Rett, fragile X, and Angelman syndrome. An April conference on the Disorders of Synaptic Dysfunction, drew leaders in the field along with Dr. Story Landis, director of the National
Without that enzyme, he could not make arginine, a critical amino acid. Arginine plays an important role in the urea cycle, which enables the body to avoid the toxic buildup of the materials that can make ammonia. A buildup of ammonia in the body damages the body’s organs, including the brain.
Giving Jonathan arginine prevented the damaging buildup of ammonia, but by age 3, he was experiencing two other symptoms—high blood pressure and neurodevelopmental delay. Lee and mem bers of his laboratory sought to find out why these problems con-tinued in Jonathan and others like him. In November 2011, they published their results in the journal Nature Medicine.
“Arginine is the single amino acid in the body that makes nitric oxide,” said Lee, a Howard Hughes Medical Institute Investigator. The problems Jonathan suffered were what one would expect from a deficiency in nitric oxide. What Lee and his colleagues discovered was that because Jonathan lacked the enzyme argininosuccinate lyase, he not only could not make arginine, he also could not use the arginine he received to make nitric oxide. The enzyme plays a dual function. The first is to make arginine and the second is to hold together a complex of proteins that transfers arginine to the part of the cell where it can make nitric oxide.
Lee talked to his team and decided that they knew how to treat the problem based on their work in the laboratory and with mice. He asked Jamie Oliphint, Jonathan’s mother, to have him admitted to Texas Children’s. There Nagamani helped wean him off his ineffective blood pressure medicine and started him on a nitrate.
“Over a period of four days, his blood pressure and pulse became normal,” said Lee. “In the two years since, his heart has become stable. ”
“ Having an immediate impact on the life of a child is the most rewarding feeling.” Dr. Brendan Lee
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Insel said the key might be in understanding what “we really know about autism.”
“Is the autistic behavior we see in fragile X the same as the social deficits of autism?” he asked. Studies have shown that idiopathic autism may involve genes of synaptic pro-teins, high rates of copy number variations as well as de novo changes in genes. What do these mean?
“We all have many mutations. On average, we have 20 to 25 loss-of-function mutations that are heterozygous,” said Insel. “We are all knockouts. How do you distinguish the ones that show up in autism.”
He also advised looking for ways to deal with the most difficult symptoms of autism—irritability, sleep problems, stomach pains and attention deficit hyperactivity disorder.
“It does not have to be a magic bullet,” he said. “For some parents of daughters with Rett, they would be pleased if their children had purposeful hand movement.” •
Institute of Neurological Disorders and Stroke, and Dr. Thomas R. Insel, director of the National Institute of Mental Health.
The conference was both a display of current knowledge and a series of brainstorming sessions to determine where to go next. Zoghbi and Dr. Morgan Sheng, vice president for Neuroscience at Genentech, organized the event, joined by editors of Science Translational Medicine. Sponsors included the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital (NRI) and Baylor College of Medicine. Zoghbi is director of the NRI and a professor of neurology, neuroscience, pediatrics and molecular and human genetics at BCM. She is also a Howard Hughes Medical Institute Investigator.
In some instances, the promise of new knowledge is tantalizingly close. In fragile X, research has taken the discovery of the fragile X gene by Dr. David Nelson, professor of molecular and human genetics at BCM, Dr. Steve Warren at Emory University, and others at BCM to an understanding of how the protein involved represses production of receptors that are necessary at the synapse—where information is transmitted from one neuron to the next. Clinical studies in people are underway using drugs to block this chemical signal.
The research at the genetic, molecular and cellular levels has been elegant and eye-opening, but the next step is to translate it to people, Zoghbi reminded the conferees.
She and leaders from the pharmaceutical industry also said science needs to take more caution.
“Failure can come from scientists doing limited preclinical studies and publishing an overstated conclusion about that clinical application,” Zoghbi said.
As a resident, Dr. Huda Zoghbi (left) first met Ashley Fry, the young girl in this photo with her parents. Ashley, who suffers from Rett syndrome, inspired Zoghbi to pursue research on this disorder. Ashley and her parents were special guests at a luncheon at the medical conference organized to brain-storm new ways to attack Rett and other disorders of synaptic dysfunction.
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However, many of these ideas have potential to turn into marketable products. When that potential is great enough to capture the interest of big pharma or biotech companies the testing and development of the idea for marketing are taken over by the company.
But, what of the many innovations for which the potential market is not yet clear. Many an innovation with such potential has languished for lack of resources to bring them to market.
Baylor College of Medicine has begun taking a different approach. Referred to as
Podcos—a term coined by BCM Technologies President Caroline Popper—BCM provides a modest amount of capital and space to nascent companies so they can work closely with investigators to access potential first adopter customers and determine if there is a sustainable market for the product.
“I was trying to come up with a mechanism to get exciting new ventures off the ground in a way that conserves the use of capital and resources and yet allows the company to test the waters of the market,” Popper said.
From Bench to MarketGreat ideas arise daily in laboratories. Afterall, this is what scientists do. They develop ideas, they test ideas, they prove ideas can work. The paper is published and the researcher moves on to the next challenge.
Immuno fluores cence image of nuclear RNA processing speckles using one of several hundred monoclonal antibodies obtained from a single mouse. The patent-pending mAbVista approach ensures all new antibodies are specific, sensitive and versatile for use as research and/or biomarker probes.
9
“The idea is that BCM will support the operations of these companies for an initial 18-24 month period, after which they need to be prepared to launch from the College and sustain themselves,” said Michael B. Dilling, Ph.D., Director of the Baylor Licensing Group.
In just the first few months of launching, Podcos has spurred two new companies that are expected to generate products and services for the research market, Twister Biotech, Inc., and mAbVista, Inc.
Twister Biotech, Inc., was formed in fall 2011 to commercialize a proprietary MiniVector DNA technology developed in the laboratory of Dr. Lynn Zechiedrich, professor of molecular virology and microbiology at BCM. MiniVector DNA are very small, supercoiled DNA constructs that can be used for a variety of purposes, including gene knockdown, long term expression and cell labeling.
The company can produce customized constructs containing a customer’s sequence of interest in a molecule as small as 250 base pairs. MiniVector DNA offers a superior alternative to other platforms because these vectors can enter cells that are normally refractory to transfection and their small size results in enhanced physical and biological stability. Experimental data has shown that MiniVectors can be used to support prolonged expression of sequences of interest in mammalian cells. To learn more, check out Twister’s website at twisterbiotech.com or call Twister at 713-798-1970.
A second PodCo, mAbVista Inc., has been launched to provide custom monoclonal antibody production services and reagents. The company will leverage a technology developed by BCM investigators Drs. Dean Edwards, professor, and Michael Mancini, associate professor, both in the Department of Molecular and Cellular Biology. They created a high-throughput approach to the development of monoclonal antibodies that will be qualified for image-based screening methods.
mAbVista’s proprietary technology platform can be used for “sub-proteome” immunization using networks of proteins from cellular compartments or structures, such that collections of high quality, imaging-ready monoclonal antibodies can be produced. There are many commercially available monoclonal antibodies that aren’t suitable for more demanding applications, but mAbVista’s antibodies will all be pre-qualifed for these purposes.
The company has acquired equipment and is in the process of com mencing operations. •
TWISTER BIOTECH, INC.
Twister Biotech creates MINIVECTORS™ derived from a larger parent plasmid con tain-ing the origin and resistance genes necessary for amplifi cation in bacteria. During production, a recombination event removes all of these undesirable components to leave only the pure, minimized vector contain ing the sequence of interest.
Parent Plasmid
AntibioticResistance
Gene
Origin ofReplication
Intermediate
MiniVectorDiscarded
Sequences
From left, Meredith Brown and Christy Franco of Twister Biotech
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ROTAVIRUS INFECTION MAY DEPEND ON YOUR BLOOD TYPE
Your blood type might be the deciding factor in whether you get infected with a particular strain of rotavirus, the
leading cause of severe dehydration and diarrhea in infants around the world. According to a report by Baylor College of Medicine researchers in the journal Nature, some strains of rotavirus “bluff” their way into the cells of the gastrointestinal tract by recognizing antigens associated with the type A blood group.
In strains of rotavirus that infect animals, the top of a spike on the virus attaches to the cell via a glycan (one of many sugars linked together to form complex branched-chain structures) with a terminal molecule of sialic acid. The same did not appear to be true of virus strains that infect humans.
“We wondered how this genotype of rotavirus recognized a cellular glycan,” said Dr. B. V. Venkataram Prasad, holder of the Alvin Romansky Chair in Biochemistry at BCM and the report’s corresponding author. “With colleagues at Emory [University School of Medicine], we found that the only type of glycan that interacted with the top of the virus spike was type A histo-blood group antigen.”
In collaboration with the laboratory of Dr. Mary Estes, holder of the Cullen Foundation Endowed Chair at BCM and a member of the National Academy of Science, Prasad and his colleagues found that laboratory cells modified to express the histo-blood group antigen A were easily infected by this rotavirus strain. Cells that lacked this antigen were not easily infected.
DROSOPHILA GENETIC REFERENCE PANEL BRIDGES
GENOTYPE-PHENOTYPE GAP
Researchers now have a powerful new tool for studies seeking to discover how to predict phenotype (appearance,
behavior or other outward characteristic) from information on an organism’s genotype.
The Drosophila melanogaster Genetic Reference Panel is a living library of 168 lines of fruit flies that is now available to researchers around the world thanks to a group of scientists from North Carolina State University, the Baylor College of Medicine Human
Genome Sequencing Center and Campus Universitat Autònoma de Barcelona. A report on the panel appeared in the journal Nature.
Researchers who want to make use of the new tool can get the flies from the stock center at North Carolina State University and the genome sequences from BCM, said Dr. Stephen Richards, assistant professor in the BCM Human Genome Sequencing Center and an author of the report.
OVARIAN CANCER ARISES IN
FALLOPIAN TUBE
Dr. Martin Matzuk, vice chair and professor of pathology &
immunology at BCM, and colleagues showed that the disease that is typically called “ovarian” cancer does not arise within the ovary but instead from the fallopian tubes in mice that lack two genes—Dicer and Pten. A report on this work was published in the journal Proceedings of the National Academy of Sciences.
Mutations in these genes have recently been shown to be altered in women with high-grade serious ovarian cancer, the type that accounts for 70 percent of all deaths attributable to ovarian cancer.
“While many questions remain about the steps in the pathogenesis of this deadly disease in women, our study opens a new door to understanding its molecular origins and progression,” Matzuk said. Matzuk is the corresponding author of the report and a member of the NCI-designated Dan L. Duncan Cancer Center at BCM.
BUILT-IN GPS IN BIRDS IN TUNE WITH THE EARTH’S MAGNETIC FIELD
Birds come with their own built-in GPS system that uses the Earth’s magnetic field. Researchers at Baylor College of Medicine are now closer to understanding how they detect the magnetic force.
In a study that appeared in the journal Science and was widely covered by media around the world, Drs. Le-Qing Wu, post-doctoral fellow, and J. David Dickman, professor of neuroscience, both at BCM, showed how certain brain cells in pigeons encode the direction and intensity of the Earth’s magnetic field.
“We were able to show how neurons in the pigeon’s brain encode magnetic field direction and intensity,” said Dickman, who conducted much of the research at Washington University in St. Louis. Dickman and Wu used electrodes in one brain area, known as the vestibular nuclei, to record activity when the bird was exposed to a changing magnetic field.
“Birds give us a unique opportunity to study how the brain develops these spatial maps and the receptors that feed into it because they have such a great ability to navigate,” Dickman said.
11
ANTISENSE OLIGONUCLEOTIDES MAKE SENSE IN
MYOTONIC DYSTROPHY
Antisense oligonucleotides—short segments of genetic material designed to target specific areas of a gene or
chromosome—that activated an enzyme to “chew up” toxic RNA (ribonucleic acid) could point the way to a treatment for a degenerative muscle disease called myotonic dystrophy, said researchers from Baylor College of Medicine and Isis Pharmaceuticals, Inc., in a report in the journal Proceedings of the National Academy of Sciences.
In myotonic dystrophy, the most common muscular disease in adults, mutations in one gene lead to a build up of RNA in the cell’s nucleus. This RNA interferes in the functioning of other proteins, eventually leading to abnormal expression of many proteins and producing the disease symptoms.
To counteract this, Dr. Thomas A. Cooper, professor of pathology and immunology at BCM and colleagues created antisense oligonucleotides called gapmers, which are simply strands of genetic material that seek out portions of abnormal RNA and target an enzyme that destroys the toxic RNA. They successfully tested this approach in cell culture as well is in mice models of myotonic dystrophy.
FROM CIGARETTE TO EMPHYSEMA
From the cherry red tip of a lighted cigarette through the respiratory tract to vital lung cells, the havoc created
by tobacco smoke seems almost criminal, activating genes and portions of the immune system to create inflammation that results in life-shortening emphysema, said researchers led by those at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center.
“These studies show for the first time that emphysema is caused by a specific immune response induced by smoke,” said Dr. Farrah Kheradmand, professor of medicine and immunology at BCM and a senior author of the report.”It’s like walking into a crime scene.”
In a report in the journal Science Translational Medicine, the scientists described the track toxic smoke takes through the tissues and how it accomplishes its destructive work. Kheradmand and colleagues showed that the cigarette recruited antigen-presenting cells (cells that orchestrate the immune system’s response to antigens) as co-conspirators in the lung-destroying crime, using specific genes that regulate proteins in their deadly role.
12
TRANSCRIPTION FACTOR CHURNS VICIOUS CYCLE
BEHIND TYPE 2 DIABETES
A transcription factor activated by too much sugar in the blood is a driver of an implacable cycle of too little insulin
resulting in too much sugar in the blood that, in turn, causes failure of beta cells to make enough insulin which results in even higher blood sugar and type 2 diabetes, said researchers from Baylor College of Medicine in an report in the journal Diabetologia.
That transcription factor—carbohydrate response element binding protein or ChREBP—offers the possibility of a target for drug treatment for the disorder that affects as many as 25 million people in the United States, said Dr. Lawrence Chan, director of the federally funded Diabetes and Endocrinology Research Center at BCM and chief of the section of diabetes, endocrinology and metabolism in the BCM Department of Medicine.
BREAKING ONCOGENE ADDICTION
Humans have no monopoly on addiction. Cancers can become addicted to certain genes and this addiction ensures
their continued growth and dominance.
Exploiting this addiction to rid the body of cancer was the rationale for research pursed by scientists at Baylor College of Medicine and Harvard Medical School. Their work gives treatment a new direction that could kill the cancer without harming normal tissue. A report on their work appeared in the journal Science.
“The fundamental question we asked was how are the stresses in cancer cells different from those in normal cells?” said Dr. Thomas Westbrook, assistant professor of molecular and human genetics and biochemistry and molecular biology at BCM and a senior author of the report.
The researchers were able to identify an enzyme crucial to survival of a type of breast cancer cell that is dependent upon the oncogene myc. When they turned off this enzyme in mice their tumors stopped growing and many of them melted away.
“If you inhibit this enzyme in a breast cancer not driven by myc, nothing happens,” said Westbrook. “If you inhibit it in normal cells of many kinds, nothing happens.”
That means that turning this enzyme off may be a great way to kill off cancers without many of the side effects of traditional chemotherapies.
NEW THEORY OF GENETIC DISEASE
Until recently, genetic and genomic diseases were classified based on their
origins. Mendelian, or single-gene, diseases had mutations in single genes. Genomic disorders originated with chromosomal duplications or deletions that affected the integrity of genes and their controllers. Genome-wide association studies look for common variations in genes that could be associated with chronic diseases.
In a paper published in the journal Cell researchers proposed a unified picture where all kinds of genetic variation—changes in single genes (single nucleotide polymorphisms or SNPs), deletions or duplications of a large part of chromosomes (copy number variation), rare genetic variants, common variants—all play a role in a person’s biologic continuum, health and risk of disease.
The authors include Dr. James Lupski, vice chair of molecular and human genetics at Baylor College of Medicine; Dr. Richard Gibbs, director of the Baylor Human Genome Sequencing Center; Dr. John Belmont, professor of molecular and human genetics at BCM, and Dr. Eric Boerwinkle, professor and director of the division of epidemiology at The University of Texas School of Public Health at Houston.
“By trying to capture all variations rather than focusing on only one gene, one individual or one tool, you can understand the role of genetic variation in disease susceptibility more completely,” said Lupski.
Gibbs and Lupski said they hoped the paper encourages discussion about the best way forward in understanding disease and its genetic underpinnings.Funds for this publication were provided by the
BCM President’s Circle.
CH2OH
HEADING TO SAN FRANCISCO FOR THEAAMC NATIONAL MEETING?
Join Dr. Paul Klotman, President and CEO of Baylor College of Medicine,at the BCM Alumni and Friends Reception
SAVE THE DATE
AAMC NATIONAL MEETING
6:30 PM to 8:00 PMMarriott Marquis
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The reception is open to all alumni and friends of BCM. You do not need to be registered for the AAMC Annual Meeting to attend.
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