Wolverine Foundation Research Team

The Wolverine Foundation has assembled a community of researchers who are working together to fulfill the foundation’s goals of defining disease mechanisms, determining impacts of MAPK8IP3 genetic variants, and discovering drug therapies. In order to accomplish these goals, researchers are using a variety of cell and animal models to assist in experimental hypothesis testing and drug discovery. Human embryonic kidney (HEK), patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 modified worms, zebrafish, and mice models of patient variants are all being developed in order to assure that all avenues of research are explored. Models being created will be made available to the research community for future collaborations and experiments to continually expand research into MAPK8IP3 genetic disease.

The Wolverine Foundation is currently engaging in a variety of innovative and cutting edge initiatives to expand research into MAPK8IP3 genetic disease studies to address this issue, but we are constantly seeking out new, innovative  and cutting edge research initiatives.  The Wolverine Foundation (“WF”) is sponsoring the following research studies which are investigating possible treatments for the MAPK8IP3 genetic mutation.

Research teams

The Anderson Lab at BIDMC

Dr. Anderson

Dr Matthew P. Anderson, MD, PhD, is an Associate Professor and Principal Investigator in the Departments of Pathology, Neurology and Director of Neuropathology at Beth Israel Deaconess Medical Center. He is creating various mouse models of this specific mutation to understand how the mutant protein causes significant deficits in fine and gross motor and cognitive skills and to test potential therapies aimed at reversing these deficits.

About Dr Anderson →

Matthew P. Anderson, M.D., Ph.D. is Director of Neuropathology, Beth Israel Deaconess Medical Center; Neuropathologist of Autism BrainNet; and Faculty, Harvard Medical School Neuroscience PhD Program. He won the International Distinguished Dissertation Award (top PhD thesis in science in U.S.A. and Canada, awarded once every 5 years) for seminal work with HHMI Investigator Michael Welsh by uncovering the ion channel and regulatory functions of the cystic fibrosis gene product and the mechanisms of disease-causing mutations [published in Cell, Science (4), Nature (2), and PNAS (2)]. His postdoctoral fellowship at Massachusetts Institute of Technology with Nobel Laureate Susumu Tonegawa (somatic recombination to generate immune receptor and antibody diversity) led to training in immunology, neuroscience, Cre-LoxP conditional mouse molecular genetics, brain slice electrophysiology and synaptic physiology, in vivo electrophysiology, and behavioral neurosciences. At Harvard, his laboratory leverages these technologies to investigate the molecular, immunologic, and neuronal circuit basis of genetic forms of human neurological and psychiatric disease including autism spectrum disorder, intellectual disabilities, and epilepsy.

His laboratory identified the first human genetic epilepsy disorder with defective postnatal developmental pruning and maturation of glutamatergic circuits (Zhou et al. Nature Medicine 2009). They created the first genetic mouse model (Smith et al. Science TM 2011) of a frequent and strongly penetrant genetic autism spectrum disorder [maternal 15q11-13 triplications, idic(15); Glessner et al. Nature 2009; Finucane et al. Gene Review 2016]. Increased Ube3a gene dosage alone (a 15q11-13 gene expressed exclusively from the maternal allele in neurons) reconstituted the behavioral deficits resembling those in human autism (impaired social interaction and vocalization and increased repetitive behavior). We also reported that mice with maternal Ube3a deletions, modeling Angelman syndrome where there is clinical evidence of increased social motivation, are hypersocial in the same paradigms where mice with increased Ube3a gene dosages have impaired sociability (Stoppel et al. Experimental Neurology 2017). Maternal Ube3a deletion occluded the hypersociability triggered by brief periods of social deprivation. 

These findings establish UBE3A dosage strongly regulates social behaviors. Recently (Krishnan et al. Nature 2017), they applied transcriptional profiling, protein interaction network analysis, Cre-loxP conditional genetics, stereotaxic viral vectors, chemogenetics, and optogenetics to map the sociability deficits characteristic of autism that they found result from the actions of increased UBE3A in the cell nucleus They discovered that UBE3A and seizures synergize to repress Cbln1 gene expression and impair sociability. Cbln1 encodes a secreted synapse organizing protein that bridges presynaptic neurexin (Nrxn1) and postsynaptic glutamate delta receptor (Grid1), two genes deleted in autism. Loss of Cbln1 disrupts synapses of previously enigmatic glutamatergic neuron in the mesolimbic motivation circuits of the ventral tegmental area (VTA) to impair social behavior. We have also discovered that increased UBE3A generates elevated aggression in mice modeling the irritability found in autism. We have defined the specific synapse where NRXN1-CBLN1-GRID1 transsynaptic complex defects give rise to the elevated aggression in this mouse providing further evidence for the role of this molecular pathway in the pathogenesis of behavioral phenotypes. Enabled by his role at clinical neuropathologist for Autism Brain Net, his laboratory recently reported the novel discovery of T-cell immune dysregulation in about 65% of postmortem cases of autism spectrum disorder including evidence for the cytotoxic T-cell attack of the astrocyte CSF-brain barrier formed by glia limitans (DiStasio et al. Annals of Neurology 2019). A completely novel histopathologic feature the astrocyte membranous blebs correlated in quantity with the number of lymphocytes across the autism cases.

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BIDMC Team

Weipang Chang

About
My research focuses on synaptic plasticity, the lifelong amazing capacity to change and adapt in light of internal and external environmental modifications.The long-term goal of my research is to investigate the mechanism of synaptic plasticity changes in various neurological disorders, and to discover treatments by modulating synaptic plasticity that restore homeostasis to a diseased brain.

 

The Ferguson Lab at YSM

Dr. Ferguson

We are supporting Dr Shawn Ferguson, PhD Associate Professor of Cell Biology and Neuroscience at Yale on his research that will use human neurons derived from induced pluripotent stem cells (iPSCs) as a platform for the identification of candidate therapeutic strategies to treat disabilities arising from MAPK8IP3 deficiency. Shawn is engaging in our most concentrated protein characterization study of this mutation. 

About Dr Ferguson →

PhD, Associate Professor of Cell Biology and Neuroscience.  Dr. Ferguson earned his Ph.D in Neuroscience from Vanberbilt University in 2004 and subsequently pursued postdoctoral studies at Yale University. Both of these training experiences focused on specialized membrane trafficking mechanisms that support synaptic transmission between neurons.

In 2010, he established his independent laboratory in the Department of Cell Biology at Yale School of Medicine which focuses on the intersection between fundamental cell biology questions and neurological disease mechanisms He currently holds the rank of Associate Professor (tenured) and has a secondary appointment in Neuroscience.

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The Chung Lab at CUIMC

Dr. Chung

We are working with Dr Wendy Chung, MD, PhD Chief, Division of Clinical Genetics, Department of Pediatrics at Columbia to help support a patient registry and natural history study collection for this mutation.

About Dr Chung →

Dr. Wendy Chung is an ABMG board certified clinical and molecular geneticist with 20 years of experience in human genetic research of monogenic and complex traits including diseases such as breast cancer, pancreatic cancer, congenital heart disease, pulmonary hypertension, inherited arrhythmias, cardiomyopathies, obesity, diabetes, congenital diaphragmatic hernias, and autism. She has extensive experience mapping and cloning genes in humans, and describing the clinical characteristics and natural history of novel genetic conditions and characterizing the spectrum of disease, and developing tailored care and treatments for rare genetic diseases.

Dr. Chung directs NIH funded research programs in human genetics of birth defects including congenital diaphragmatic hernia, congenital heart disease, and esophageal atresia, autism, neurodevelopmental disorders, pulmonary hypertension, cardiomyopathy, obesity, diabetes, and breast cancer. She leads the Precision Medicine Resource in the Irving Institute at Columbia University and is a member of the National Academy of Medicine. She has authored over 450 peer reviewed papers and 75 reviews and chapters in medical texts. 

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CUIMC Team

Alexa Geltzeiler

About
Lecturer in Genetic Counseling, Department of Pediatrics, Fieldwork Supervisor: General Genetics, Genetic Counselor Columbia University Irving Medical Center.  Alexa completed her genetic counseling graduate education at Johns Hopkins University/NHGRI. She is an ABGC board-certified genetic counselor in the Division of Molecular Genetics and her clinical work is focused on rare genetic disease in childhood. Alexa also serves as a research coordinator for Simons Searchlight, working with scientists and families to find genetic answers to autism and related neurodevelopmental disorders. Alexa works directly with the WF Team on a weekly basis to synthesize and streamline updates from the Columbia research initiatives.

 

The Gowrishankar Lab at UIC

Dr. Gowrishankar

We are sponsoring Dr. Swetha Gowrishankar Assistant Professor in the Department of Anatomy and Cell Biology at The College of Medicine at The University of Illinois Chicago.  Her initiative is focused on evaluating efficacy of candidate compounds for rescuing lysosome defects in MAPK8ip3 KO iNeurons.

About Dr Gowrishankar →

Swetha Gowrishankar, Ph.D., is an Assistant Professor at the Department of Anatomy and Cell Biology at the University of Illinois at Chicago (UIC). She is a Faculty Fellow of the Honors College and Faculty of the Graduate Program in Neuroscience, UIC. She has over fifteen years of experience investigating lysosome biology which includes her post-doctoral work studying axonal lysosome transport in the laboratories of Shawn Ferguson and HHMI Investigator Pietro De Camilli at Yale School of Medicine. She was a recipient of BrightFocus fellowship for research on Alzheimer’s disease and Cayman Woman in Research Grant. At UIC, her lab studies mechanisms underlying lysosome formation and function in neurons as well as mechanisms underlying lysosome dysfunction in neurodegenerative diseases such as Alzheimer’s disease and Hereditary Spastic Paraplegia. She addresses these questions using a multidisciplinary approach (imaging, biochemical techniques and proteomics) in mouse models of these diseases as well as iPSC-derived neurons.

The Precision Medicine Institute at UAB

Dr. Might

We are working with Dr Matt Might, PhD, Director Hugh Kaul Precision Medicine Institute University of Alabama and his team, sponsoring zebrafish and c elegan research studies. His team will also be responsible for developing Transcriptomic profiling (RNA-sequencing) of MAPK8IP3 patient-specific iPSC-derived neurons We are intrigued and interested by Dr Matt Might’s current research in biomedical informatics.

About Dr Might →

Director, Hugh Kaul Precision Medicine Institute and Professor, UAB School of Medicine.  Dr. Might has been the Director of the Hugh Kaul Precision Medicine Institute at the University of Alabama at Birmingham (UAB) since 2017. At UAB, he is the Hugh Kaul Kaul Endowed Chair of Personalized Medicine, a Professor of Internal Medicine and a Professor of Computer Science. His research at UAB focuses on precision prevention, diagnosis, and therapeutics across rare disease, cancer and common/chronic conditions. A principal theme in his research is the use of computer and data science to enhance clinical and academic medicine.

From 2016 to 2018, Dr. Might was a Strategist in the Executive Office of the President in The White House. At The White House, he worked primarily on President Obama’s Precision Medicine Initiative with both the NIH and the Department of Veterans Affairs. In 2015, Dr. Might joined the faculty of the Department of Biomedical Informatics at Harvard Medical School as a visiting professor. At DBMI, his research focused on rare disease discovery and diagnosis, and on the development of personalized therapeutics for rare disease.

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UAB Team

Dr. Crowder

About

Cammie joined UAB’s Hugh Kaul Precision Medicine Institute as the Assistant Director of Education, Research, and Science Communication in 2020. As a senior laboratory scientist at PMI, she uses CRISPR-Cas9 mutagenesis to develop patient-guided zebrafish models of rare-genetic disorders associated with neurodevelopmental and neuropsychiatric disease. Through her research, she aims to describe molecular mechanisms contributing to patient symptoms and complete drug screens in zebrafish models to identify potential therapeutic options that could be repurposed to treat patients. She uses research in her teaching and has developed a series of laboratory-based curriculum for UAB undergraduate programs in the areas of genetics, molecular biology, and precision medicine. Cammie is also a medical writer and has a passion for communicating science to a wide range of audiences serves as a technical and grant writer for PMI. 

Prior to her current position, she was awarded an NIH Institutional Research and Academic Career Development Award (IRACDA) and completed her postdoctoral fellow at UAB examining endocrinological disease and rare-human genetic disorders in the labs of Dr. Daniel Gorelick and Dr. Matt Might. She received her PhD in 2016 from Oregon State University in Corvallis, OR. She is originally from Birmingham, AL.

 

Dr. Yeo

About
Dr. Yeo currently is an Instructor and is on research faculty in the Department of Pharmacology and Toxicology, and Precision Medicine Institute at the University of Alabama, Birmingham. During her graduate studies, Dr. Yeo worked with Dr. Howard Jacob at Medical College of Wisconsin, where she used genetic mapping, functional and comparative genomics to identify novel genes for cardiovascular diseases. For her postgraduate work, Dr. Yeo worked with Dr. George Church at Harvard Medical School to study genome repair and engineering. Her work subsequently led to the development of several computational software and synthetic tools that enhance methods of gene editing using CRISPR-Cas9 technologies. Towards her independent research program at UAB, her current work capitalizes on the CRISPR tools she built during her postgraduate studies to investigate the genetic basis of human diseases, with a strong interest in studying the genetic regulation of cell stress and genomic instability. She will support research at the WF by developing genome-edited induced pluripotent stem cells derived from patients and using transcriptomic sequencing approach to identify dysregulated pathways in patient-derived neurons.

 

Dr. Yoder

About

Dr. Bradley K. Yoder is a Professor and Chair of the Department of Cell, Developmental, and Integrative Biology in the School of Medicine at the University of Alabama at Birmingham (UAB).  He holds the UAB Health Science Foundation Endowed Chair in Biomedical Research and was the 2019 recipient of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease. He is the Director of the NIH funded Childhood Cystic Kidney Disease Center, Co-director, with Dr. Matt Might, of the NIH funded Center for Precision Animal Modeling (C-PAM), and the Director of the Graduate Training Program in Cell, Molecular, and Developmental, Biology. He joined the faculty at UAB in 1997 after completing his postdoctoral studies at Oak Ridge National Laboratory under the guidance of Dr. Rick Woychik, where Dr. Yoder was an Alexander Hollaender Distinguished Postdoctoral Fellow.  He received his Ph.D. in molecular and cellular biology from the University of Maryland Baltimore County in 1993. 

His research focus is on the cellular and molecular mechanisms regulating assembly, maintenance, and function of the primary cilium utilizing complementary approaches in rats, mice, C. elegans, and cell culture models.  Utilizing genetic screens in C. elegans, his group identified multiple proteins required for ciliogenesis and cilia mediated sensory and signaling activities and have extended these studies into mammalian systems demonstrating critical roles for the cilium in embryogenesis and for maintaining normal tissue function in adults.   His studies have uncovered a novel role of neuronal cilia in regulating feeding behavior and satiation response that when disrupted leads to obesity and diabetes. His group has contributed to the identification of several new loci involved in human cilia related diseases. In summary, the research conducted by his group is providing innovative insights into how cilia are constructed and how they are established as a unique signaling and sensory structure with a distinct protein composition from the rest of the cell membrane.

 

Dr. Haycraft

Dr. Crouse

The Yu Lab at BCH

Dr. Yu

Dr Tim Yu, Attending Physician, Division of Genetics and Genomics, Boston Children’s Hospital and Associate Professor of Pediatrics, Harvard Medical School,  has started initial research to establish patient-derived induced pluripotent stem cells (iPSC) based neuronal models to study the neurodevelopmental phenotype associated with MAPK8IP3 variants. 

About Dr Yu →

Dr Tim Yu – MD, PhD. Dr. Tim Yu is a neurologist and researcher in the Division of Genetics and Genomics at Boston Children’s Hospital, Associate Professor of Pediatrics at Harvard Medical School, and Associate Member of the Broad Institute of MIT and Harvard. His research group works at the intersection of genetics, neurobiology, and bioinformatics to explore the basis for neurologic disease and advance genomic medicine. Research interests range from large-scale computational analyses to uncover genes responsible for autism and rare pediatric neurogenetic disorders, to the application of whole genome sequencing for early detection of disease in newborns, to pioneering the development of individualized genomic medicines.

BCH Team

Dr. Demirbas

About
Didem Demirbas, Ph.D., FACMG, is a postdoctoral researcher in Yu Laboratory in the Division of Genetics and Genomics at Boston Children’s Hospital. Didem is a broadly trained molecular biologist and a board-certified clinical biochemical geneticist with a research focus on inborn errors of metabolism and neurodevelopmental disorders. She has extensive experience with disease modeling using induced pluripotent stem cells, differentiated neurons, and cerebral organoids. She is particularly interested in learning how Mendelian genetic defects lead to disease states in humans and how to translate this knowledge for developing novel therapies, especially for orphan diseases.

 

Megan Seferian

About
Megan is a research assistant in the Yu Lab and received her Bachelor Of Science in Pathobiology and Molecular Cell Biology from The University of Connecticut. She is very interested in studying the pathophysiology of individualized gene therapies and plans to apply to medical school while continuing to pursue her research.

 

We are always eager to learn more and are constantly seeking new insights into this genetic mutation.  Please send your inquiries to research@wolvfdn.com

Are you a parent or caregiver of a patient who has been diagnosed with MAPK8IP3-related genetic disorder?

Patients & Caregivers

Research 

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