Kahle Laboratory

Human genetics and molecular mechanisms of pediatric neurosurgical disorders

SOX2 staining (pink) showing neural stem cells lining the embryonic brain ventricles in an E15.5 mouse brain section

About Our Research

The Kahle Lab conducts both human genetic and basic science research. Our research relies on the enthusiasm and generosity of the patients and families who volunteer to be a part of our work. Participants who contribute to our research gain knowledge about their own condition and enter a community of committed caregivers, passionate scientists, and other concerned parents. The overarching goal of our work is to translate basic science advances into better options for the diagnosis, management, and treatment of pediatric neurosurgical diseases and, in the process, train the next generation of neurosurgeon-scientists.

 

We are interested in the fundamental mechanisms directing human brain development that are relevant for pediatric neurosurgical diseases. These historically understudied conditions, treated with invasive and often morbid brain surgeries, include congenital hydrocephalus, Chiari malformation, cerebrovascular anomalies, and other structural brain malformations. By studying individuals and families affected with these conditions, and identifying the associated genes and their mutations, we can learn about the biological mechanisms that are important for development of the human brain, and identify potential therapeutic targets.

We necessarily employ a multidisciplinary approach that brings together neurosurgeons, neuroradiologists, pediatricians, neurologists, and basic scientists. We use human genetics (next-generation sequencing) coupled with the modeling of discovered mutations in systems such as mouse and fish. In these animals, we utilize physiology, cell biology, and biochemistry to study the pathogenic mechanisms and therapeutic vulnerabilities of specific patient mutations, including those of patients we treat in our own operating rooms.

Studies

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Cerebrospinal Fluid Disorders

Neurovascular Disorders

Cerebrospinal Fluid (CSF) disorders are conditions that affect the clear fluid that supports the brain and spinal cord. CSF disorders are a major cause of morbidity and mortality in children, but the cellular and molecular etiology remain largely unknown for most and treatment options are limited. Our lab aims to gain insight into the molecular pathogenesis of these disorders that can lead to improvements in diagnosis, prognostication, and treatment of CSF disorders.

Neurovascular disorders are conditions that affect the blood vessels in the brain or spinal cord. Although these disorders are a major cause of morbidity and mortality in children, the cellular and molecular etiology remain largely unknown for most and treatment options are limited. Our lab aims to gain insight into the molecular pathogenesis of these disorders that can lead to improvements in diagnosis, prognostication, and treatment of neurovascular disorders.

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Rare Neurological Disorders

Rare neurological disorders can encompass a wide variety of conditions affecting the brain and spinal cord. Due to their relative rarity, the cellular and molecular etiology of these syndromes remain largely unknown. This provides limited knowledge and treatment options for patients and providers. Our lab aims to gain insight into the molecular pathogenesis of these conditions that can lead to improvements in diagnosis, prognostication, and treatment of rare disorders. We are currently studying Moebius Syndrome and hope to study other rare neurological disorders in the near future.