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Child Health Institute of New Jersey

Biography

Dr. Max Tischfield is an assistant professor in the Department of Cell Biology and Neuroscience, Rutgers School of Arts and Sciences. He earned his BA degree from Rutgers College, was a member of the General Honors Program, and was a Henry Rutgers Thesis Scholar in the Department of Cell Biology and Neuroscience. Dr. Tischfield began his research career as an undergraduate student with Dr. James Millonig at the Center for Advanced Biotechnology and Medicine, where he studied transcriptional control of cerebellar development and received the outstanding undergraduate award. As a graduate student with Dr. Elizabeth Engle in the Department of Neurobiology at Harvard Medical School, he cloned and functionally characterized a series of human gene mutations that are critical for the development of the brain and surrounding blood vessels. His pioneering work helped define the human tubulinopathy field, which are a wide spectrum of cortical and brainstem malformations that result from gene mutations in the microtubule cytoskeleton. In 2005, Dr. Tischfield received the National Pre-doctoral Finalist Award by the American Society of Human Genetics in recognition of his work. During his post-doctoral studies at Johns Hopkins Medical School (Jeremy Nathans) and Boston Children's Hospital (Elizabeth Engle), Dr. Tischfield used mouse genetics to investigate the requirement of Wnt/Beta-Catenin signaling for blood barrier development and maintenance. He also characterized dural cerebral vein malformations in children with TWIST1 mutation-positive craniosynostosis, and discovered that paracrine BMP signaling from the developing skull and dura is critical for the growth and remodeling of the dural venous sinuses. Alongside this work, Dr. Tischfield continued to investigate nervous system development, with a strong emphasis on cranial motor neurons and pediatric brainstem disorders.

 

Research Interests

My research program integrates human and mouse genetics with systems biology approaches to investigate the cellular and molecular bases of human developmental disorders. During my graduate and postdoctoral training with HHMI investigators Elizabeth Engle (Harvard Medical School) and Jeremy Nathans (Johns Hopkins School of Medicine), I studied how signaling ligands, receptors, transcription factors, and cytoskeletal proteins control different cellular processes that pattern the skull, nervous system, and surrounding blood vessels. My novel discoveries helped inform the genetic and mechanistic underpinnings of six different human craniofacial, neurovascular, and neurological disorders.

  • Human and mouse genetic approaches to investigate the pathogenesis of neurodevelopmental and neurovascular disorders
  • Tourette Association of America Young Investigator Award to investigate circuit mechanisms and cholinergic interneuron dysfunction in Tourette Syndrome
  • Brain and Behavior Research Foundation Young Investigator Award to investigate basal ganglia

 

 

Research Summary

His research utilizes human and mouse genetics to decipher protein functions, signaling pathways, and cellular interactions that regulate normal mammalian development and the pathogenesis of human disease. His lab provides a multi-disciplinary research program that focuses on: (1) deciphering mechanisms that regulate the growth and functions of meningeal lymphatic vessels and the brain’s perivascular waste clearance system; (2) mouse models of neurodevelopmental and psychiatric disorders, with a particular focus on circuit mechanisms that underlie the neuropathogenesis of Tourette syndrome; (3) how meningeal malformations affect cortical development. Techniques used in his laboratory include (but are not limited to): mouse genetics, stereotactic brain injections and viral transduction, slice electrophysiology, tissue clearing and high-resolution imaging, optogenetics, and mouse behavior. Dr. Tischfield also places a strong emphasis on the mentoring and education of undergraduate, graduate, and post-doctoral fellows.

We have two primary research interests.

The first is devoted to investigating genetic, cellular, and circuit mechanisms that underlie Tourette Syndrome and comorbid conditions, including ADHD, OCD, and Autism Spectrum Disorder. My lab is a member of the Tourette International Genetics Consortium, an international multicenter collaboration focused on identifying familial and de novo gene variants. By identifying gene variants with large effect sizes, this allows us to establish animal and cell models to facilitate a better understanding of the underlying pathophysiology. My lab has engineered an allelic series of mouse models that possess human mutations in high confidence risk genes linked to Tourette Syndrome (CELSR3, OPA1, and WWC1). From a functional genomics standpoint, our goal is to understand how gene mutations affect protein function, neuronal structure, and synapse formation using anatomical and circuit-tracing techniques combined with confocal and super resolution microscopy. From a circuit standpoint, we use slice electrophysiology, optogenetics, fiber photometry, and behavior to understand how functional changes at synapses affect different loops that form cortico-basal ganglia-thalamocortical circuits.


The second major focus of my research program centers on developing innovative models and approaches to understand how skull development integrates with cerebrospinal fluid hydrodynamics, the cerebrovasculature, and brain health and function. My approach to craniofacial biology stems from my broad training in craniofacial genetics, neuroscience, and neurovascular biology, which has provided a very unique skillset to address these novel questions. Short-term goals will elucidate how craniosynostosis affects pressure and fluid forces that influence the development of brain waste clearance pathways (glymphatic system) and meningeal lymphatic vessels. These goals support a broader vision to understand how craniofacial disorders affect the functions of the glymphatic/lymphatic systems, including regulation of waste clearance and immune surveillance, and how these processes normally integrate to support craniofacial and brain health across the lifespan.

Featured Publications

  • Ang PS, Matrongolo MJ, Tischfield MA. The growth and expansion of meningeal lymphatic networks are affected in craniosynostosis. Development. 2022 Jan 1;149(1):dev200065
  • Poppi LA, Ho-Nguyen KT, Shi A, Daut CT, Tischfield MA. Recurrent implications of striatal cholinergic development in a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorder. Cells. 2021 Apr 15;10(4):907
  • Tischfield MA*, Robson CD, Gilette N, Chim SM, Sofela FA, DeLisle MM, Gelber A, Barry BJ, MacKinnon S, Dagi LR, Nathans J, Engle EC*. Cerebral vein malformations result from loss of Twist1 expression and BMP signaling from skull progenitor cells and dura. Developmental Cell. 2017 Sep 11;42(5):445-461*co-corresponding author *featured article and cover
  • Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C, Demer JL, Robertson RL……Gupta ML Jr, Pellman D, Engle EC. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell. 2010 Jan 8;140(1):74-87.
  • Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan WM, Andrews C, Erickson RP, Engle EC. Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular