Rose F. Kennedy Intellectual and Developmental Disabilities Research Center

Featured Investigator: Judy L. Aschner, M.D.

Dr. Aschner is the recently appointed physician-in-chief and chair of pediatrics at The Children’s Hospital at Montefiore (CHAM), and professor and chair of pediatrics at Einstein. Dr. Aschner’s previous appointments were director of neonatology and the Julia Carell Stadler professor of pediatrics at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University School of Medicine. Dr. Aschner is an internationally recognized leader and physician-scientist in pediatrics, neonatology and perinatal biology. She has collaborated with institutions across the United States and around the world to improve perinatal care, to mentor the next generation of neonatologists and to ensure the health of infants and children.

Dr. Aschner’s laboratory and translational research focus is on the regulation of the newborn pulmonary circulation. Her work has helped elucidate factors that contribute to altered lung development and pulmonary hypertension in infants with lung and heart disease. Her clinical interests include prevention of chronic lung disease (bronchopulmonary dysplasia), treatment of infants with pulmonary hypertension, optimizing nutritional management of premature infants and prevention of prematurity. She has translated her bench work to the clinical arena where she is currently a principal investigator on a National Heart, Lung, and Blood Institute-funded multi-center study to identify novel biomarkers that predict which extremely preterm infants are at greatest risk for long-term respiratory morbidity. Moving forward, Dr. Aschner has expressed keen interest in fostering greater research at Einstein/CHAM in the area of premature births. Dr. Aschner has also already moved to further strengthen the Children’s Evaluation and Rehabilitation Center (CERC) at Einstein and its close ties to the IDDRC program. Clearly, Dr. Aschner is yet another indication of the renaissance of IDD research at Einstein, and one in which our newly configured Rose F. Kennedy Center will prosper.

(Posted June 2013)
 

 

Previously Featured Investigators

Dr. Aleksandra Djukic: Neurophysiology of Receptive Speech in Rett Syndrome 

Dr. Aleksandra (Sasha) Djukic is an Associate Professor of Clinical Neurology and Pediatrics at the Albert Einstein College of Medicine and also Director of the Tri-State Rett Syndrome Center at the Children’s Hospital at Montefiore (CHAM), one of the largest Rett Syndrome clinics in the U.S. Dr. Djukic is a diplomate of the American Board of Psychiatry and of Neurology and specializes in the evaluation and treatment of children with cognitive impairment disabilities with a special expertise in girls with Rett syndrome.

According to Dr. Djukic, the Tri-State Rett Syndrome Center at CHAM was born in part from a science breakthrough a number of years ago showing that even severe symptoms of Rett syndrome in mouse models of this disorder can be reversed. With the support from the Division Chair, Dr. Solomon Moshé, another IDDRC investigator, Dr. Djukic developed the clinical Rett center at CHAM, with the hope that effective treatments could be developed for these girls. With the center now established, research collaborations have begun to blossom, in parallel with the basic science studies led by Dr. Aristea Galanopoulou, another IDDRC investigator.

Through interacting with Rett patients in the clinic, Dr. Djukic observed that the cognitive abilities of these girls may be underestimated. Dr. Djukic says “I saw the ability of these girls with Rett syndrome to communicate in ways that were hidden before.” As a case in point, through collaboration with Dr. John Foxe, Associate Director of the RFK IDDRC, a study was funded last year by NIDCD to study receptive language abilities in RETT syndrome girls using a new ‘system identification’ approach adapted from the control-engineering field, in conjunction with high-density electrophysiology. The results of such studies have highlighted the need for more customized testing for girls with Rett syndrome to more accurately assess their intellectual abilities and psychological states. It has been found that it is a medical necessity for these girls to have access to eye-gaze speech-generating computers in order for them to be able to demonstrate their mental ability and to communicate with their families. Through education and outreach the center hopes to end the perception that those with Rett Syndrome cannot learn. The center ensures that each patient have continuity of care from infancy through adolescence and adulthood.

Recently, a Rett syndrome interest group has formed which will build collaborations between neuroscientists, cell biologists, and geneticists at Einstein and clinicians at CHAM. Focus here is on both Rett patients and on animal models related to Rett syndrome. Through continued collaborative efforts, these experimental studies will hopefully translate into successful treatments. 

Anyone interested in this area of research is welcome to contact Dr. Djukic for further discussion and possible collaboration.

(Posted March 2013)
 

 

Dr. Francine Einstein: Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth 

Dr. Francine Einstein, an Associate Professor in the Department of Obstetrics & Gynecology and Women’s Health, serves as a member of the Executive Committee of the RFK IDDRC. Dr. Einstein is also the head of the epigenetics and brain development research cluster of the RFK IDDRC. In this role, she fosters communication and collaboration between geneticists and neuroscientists to better understand the gene-environment interactions that affect neurodevelopment, cognitive functioning and plasticity of the brain. She organized the first of the RFK IDDRC’s cluster workshop series, entitled The Exposome and the Developing Brain in 2011, in which IDDRC investigators and clinicians exchanged ideas, consolidated collaborations and learned of each other's work.

Dr. Einstein’s background in maternal-fetal medicine and research on aging, particularly dysregulation of glucose metabolism related to aging, lead to her interest in the fetal origin of adult disease concept (i.e., things that happen in early life can have significant impact on health later in life). With support from NICHD, Dr. Einstein is currently investigating the relationship between abnormal fetal growth and epigenetic changes. This study, which involves infants born in the Bronx who have abnormally high and low birth weights, is aimed at discovering biomarkers that would someday be used to identify those infants at increased risk for age-related diseases, such as type 2 diabetes, later in life. In her study, Dr. Einstein utilizes the Neurogenomics core, one of the six RFK IDDRC Scientific cores, to explore genome-wide DNA methylation alterations associated with abnormal fetal growth, as well as bioinformatic and systems biology support for data analysis and interpretation. According to Dr. Einstein, conditions during fetal development that alter epigenetic patterns of DNA methylation in stem cells may be a marker for, or contribute to, susceptibility to age-related diseases. Her group is also interested in improving environmental exposure assessment and exploring how ubiquitous exposures may impact on normal brain development or inhibit the attainment of full cognitive potential. 

Anyone interested in this area of research is welcome to contact Dr. Einstein for further discussion and possible collaboration.

(Posted August 2012)
 

 

Dr. Pierfilippo De Sanctis: Predicting Speech-language Deficits in Pre-lingual Infants 

Dr. Pierfilippo De Sanctis, an Assistant Professor in the Department of Pediatrics, aims to establish himself as an independent translational researcher in the study of developmental disabilities. His background is on studies probing the sensory-perceptual bases of intact sound and language processing in healthy adult populations, using cutting-edge neuroscience methodologies, including high-density electrophysiological recordings from the scalp and direct recordings from the cortical surface in epilepsy patients. His goal is to bring his expertise to bear on clinical pediatric and diagnostic issues, with an emphasis on the early detection of language impairment in children on the autism spectrum. Dr. De Sanctis is a current recipient of the pilot and feasibility award sponsored by the Rose F. Kennedy IDDRC. Through this project, Dr. De Sanctis is applying a very exciting new technology, the Auditory Evoked Spread Spectrum Analysis (AESPA), which tries to provide an objective brain response to measure the integrity of early receptive speech development in pre-lingual infants and toddlers. He proposes to adapt and optimize the AESPA technique, originally developed to extract the neural responses to uninterrupted speech in mature listeners (i.e., adults), for application in pre-lingual infants and toddlers. This is an important public heath issue as more than 7% of children fail to acquire normal speech-language skills by the age of four years.

Dr. De Sanctis firmly believes that with the new method, it might be possible to identify children at risk much earlier as currently possible. Early diagnosis of children with speech-language impairment is crucial for effective intervention, which is central for improving outcome. The aims of the project are twofold: (1) to map the developmental trajectory of the speech-induced AESPA in healthy typically developing infants and toddlers from the ages of 4 to 36 months, which will span the periods before and after speech has emerged and (2) to develop optimal stimulation parameters for evoking the AESPA response in a cohort of 12 and 24 month-old infants. The AESPA represents a low-cost EG-based method that is robust, non-invasive, and can be obtained very rapidly in the clinic. (Posted May 2012) 

 Visit Dr. De Sanctis' profile page
 

 


 Dr. Vytautas Verselis: Exploring the hemichannel properties of Cx26 mutations: a cause of syndromic deafness 

According to the National Institute on Deafness and Other Communication Disorders, over 46 million people in the United States suffer from some form of communication impairment or disorder. For over 20 years, bio-physicist and channelologist, Vytas K. Verselis, Professor in the Dominick P. Purpura Department of Neuroscience has been studying structure/function relationships and gating mechanisms of a class of channels called connexins, Cxs, which form an essential communication pathway between cells. One Cx in which he has a particular interest is connexin 26 (Cx26), a protein which is encoded by the GJB2 gene. Mutations in this gene are a major cause of pre-lingual, congenital deafness.

In the last several years, Prof. Verselis has embarked upon a new direction in his research, where he is examining the mechanistic bases of hemichannel dysfunction in Cx26 that leads to severe disorders in humans such as Keratitis-Ichthyosis-Deafness (KID) syndrome. The underlying basis of this and other related syndromes appears to be aberrantly behaving hemichannels, a relatively new mechanism of disease. The hemichannels do not participate in the formation of intercellular channels, but remain undocked and function as large, ion channels in the plasma membrane. Prof. Verselis has shown that mutant hemichannels exhibit altered gating, regulation and permeability properties, which can lead to compromised cell function and cell death.

Prof. Verselis firmly believes that intervention is a possibility if you know what is going on, "The ability to create treatments for these diseases in the future will in part come from understanding how this channel works, and what we need to do to manipulate or regulate it. By understanding the mechanistic bases of hemichannel dysfunction in Cx26, this should also give us an insight into a number of disorders in which hemichannel dysfunction may play a role such as stroke, neuropathy, atherosclerosis and congenital cataractogenesis." Prof. Verselis was recently awarded a 4-year grant by the NIH on 'Mechanisms of Gating and Permeation in Gap Junctions"', a continuation of his previous work on structure/function studies of connexins with a new focus on hemichannel dysfunction.

 Visit Dr. Verselis' profile page
 

 

Former Investigators

Dr. Roy V. Sillitoe: Decoding the Cerebellar Circuit in Health and Disease 

The RFK IDDRC’s roving reporter, Edel Flynn, recently sat down with Dr. Roy Sillitoe, an assistant professor in the Dominick P. Purpura Department of Neuroscience recruited to Einstein in 2009. Having studied cerebellar cytoarchitecture in more than 25 different species, Dr. Sillitoe’s research is now focused on determining the embryonic origins of intellectual and developmental neurological diseases. "Our current efforts focus on establishing a 'wiring diagram' that illustrates brain circuit map alterations in mouse models of autism spectrum disorders (ASD), obsessive-compulsive disorder, and inherited ataxia." Two genes of current interest are Engrailed2 (En2), which has been linked to ASD, and SLC9A6, which recently was shown to be responsible for an X-linked form of Angelman syndrome. "We know that the cerebellum is involved in motor coordination, motor learning and balance, but in more recent years, substantial evidence has emerged showing that the cerebellum also might be involved in higher brain functions including cognition and emotion." Dr. Sillitoe believes that despite progress in identifying genes that are linked to neurological diseases, "we still have a very incomplete picture of which brain regions and which neural circuits are affected in these disorders." To further investigate the developmental origins of disorders that affect the formation of brain network connections, he is using a combination of molecular genetics, neuroanatomical tract tracing, biochemistry and brain imaging.

 

 

Click here to log in