Laboratory of Joan A. O’Keefe, PhD

My expertise is in the detection of gait and balance impairments in a variety of movement disorders. I am a physical therapist with doctoral and postdoctoral training in basic neurobiology and am presently conducting clinical research investigating balance and gait in several neurodegenerative disorders.

I received my BS in physical therapy from the University of Illinois-Chicago and my PhD in anatomy and neurobiology from Loyola University Chicago. I am predominantly studying Fragile X tremor and ataxia syndrome (FXTAS), which occurs in some premutation (PM) carriers of the Fragile X (FMR1) gene.

The short-term goals of my research program are to develop an early detection model for FXTAS and identify additional molecular risk factors for developing this disorder. Together with my collaborators in movement disorders and neurology and my graduate students, I am working toward the following goals:

  • Identify quantitative markers of balance and gait impairments in PM carriers with and without FXTAS.
  • Determine the impact of executive function and cognitive interference on balance and gait function in PM carriers with and without FXTAS.
  • Determine the relationship between age, sex, executive function and FMR1 molecular variables and the presence and severity of balance and gait impairment in PM carriers with and without FXTAS.

Results of this research will help clarify neurological mechanisms underlying balance and gait deficits in FXTAS. It will also establish reliable and quantitative outcomes measures of motor impairment and provide data for future clinical trials. This research is also the first step in characterizing the longitudinal history of motor dysfunction in FXTAS from its earliest stages, thus, paving the way for establishing disease monitoring and modifying strategies in premutation carriers.

My research is relevant to the National Institute of Health’s research plan on FXS and associated disorders, which includes the following goals:

  • Validating quantitative instruments to detect early clinical signs of FXTAS and its progression
  • Identifying of molecular and clinical risk factors in individuals associated with penetrance of FXTAS
  • Defining genotype and clinical phenotype relationships in FXTAS

My second research focus, in collaboration with Dr. Elizabeth Berry-Kravis, revolves around a clinical trial related to the neurodegenerative disorder Niemann-Pick C (NPC). We are using our state-of-the-art quantitative balance and gait measures to determine the efficacy of the drug Hydroxypropyl Beta Cyclodextrin, or HPßCD, in the treatment of motor problems in children and young adults with this disorder.

We are also developing a normative database of gait and balance outcome variables using inertial sensor-based technologies that we anticipate will be very useful in the conduct of future clinical treatment trials in children and young adults with neurodegenerative disorders.

Publications

Recent select works

O’Keefe JA,  Robertson E., McAsey, A, Swanson, M, Bernard, B, Berry-Kravis E, Hall DA. Cognitive function impacts gait, functional mobility and falls in Fragile X-Associated Tremor/Ataxia Syndrome; under revision review; Gait and Posture; 2018; DOI: 1016/j.gaitpost.2018.09.005

Berry-Kravis, E, Chin, J Hoffmann, A, Winston A, Stoner R, Lagorio L, Friedmann K, O’Keefe, JA. Long-Term Treatment of Niemann-Pick Type C1 Disease with Hydroxypropyl-Beta-Cyclodextrin; Pediatric Neurology. 2018 Mar;80:24-34. PMID: 29429782

Pal G, O’Keefe JA, Robertson E, Bernard B, Anderson S, Hall DA.  Global cognitive function and processing speed are associated with gait and balance dysfunction in Parkinson’s disease; J NeuroEng and Rehab. 2016. 13(1): 94-102.

Robertson E, Hall DA, McAsey AR, O’Keefe JA.  Fragile X-associated Tremor/Ataxia Syndrome: Phenotypic comparisons with other Movement Disorders, Clin Neuropsychol. 2016; 30(6):849-900.

Hall DA,  Robertson E, Shelton AL, Losh MC, Mila M, Moreno EG, Gomez-Anson B, Martínez-Cerdeño V,  Grigsby J, Lozano R, Hagerman R, Santa Maria L, Berry-Kravis E, O’Keefe JA. 2016.  Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers, Cerebellum; 2016;15:578-586.

O’Keefe JA, Robertson E, Hall DA and Berry-Kravis E.  Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome; Cerebellum; 2016;15(4):475-82.

Hall, DA, Robertson-Dick, E, O’Keefe JA, Hadd AG, Zhou L, Berry-Kravis E.  Repeat Size and X-inactivation in the Clinical Phenotype of Fragile X Premutation Carrier Sisters; Neurol Genet. 2016; 2(1):e45. PMID: 27066582

Pal G, Robertson E, O’Keefe JA, Hall DA. The Cognitive and Motor Profile of GBA-associated Parkinson Disease:  A Review; Movement Disorders: Clinical Practice, 2015; 3: 4–8.

O’Keefe JA, Robertson E, Dunn E, Li Y, Deng Y, Fiutko A, Berry-Kravis E, Hall DA. Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X Associated Tremor/Ataxia Syndrome (FXTAS).  Cerebellum, 2015; 14(6):650-62.

Hall DA, Birch R, Anheim M,  Jonch A, Pintado E,  O’Keefe, JA, Troller J,  Hagermann RJ, Fahn S, Berry-Kravis, E, Leehey MA. Emerging topics in FXTAS.  J. Neurodev Dis. 2014; 6: 31-41.

O’Keefe JA, Espinosa-Orias A , Khan H,  Hall DA, Berry-Kravis E,Wimmer MA,. Implementation of a Novel Markerless Motion Analyses System to Quantify Hyperactivity in males with Fragile X Syndrome,  Gait and Posture, 2014; 39 (2):827-30.

Hall DA, O’Keefe JA. Clinical Neurogenetics: Fragile X-associated tremor/ataxia syndrome. Neurol Clin. 2013; 31(4):1073-84.

Hall DA, O’Keefe JA. Fragile X-Associated Tremor Ataxia Syndrome:  The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update of Treatment. Tremor Hyperkin Mov;2. Epub 2012; pii: tre-02-56-352-1.  PMID: 23439567

Additional publications

A detailed listing of O’Keefe’s publications is available on PubMed.

Students and staff

Erin Robertson

I am a graduate student in the Department of Cell & Molecular Medicine, conducting my dissertation research with Joan O’Keefe. My work is focused on the study of gait, balance and cognition in patients with movement disorders and FXTAS.

Due to overlapping motor symptom profiles and a lack of physician awareness of the disorder, FXTAS patients are often misdiagnosed as having more common neurological disorders, mainly Parkinson disease (PD) and essential tremor (ET). The primary objective of my dissertation project is to use quantitative measures of gait, balance and tremor during single and dual cognitive-motor interference tasks in conjunction with cognitive assessments of executive function and processing speed to identify sensitive measures for distinguishing patients with FXTAS from patients with PD and ET. As FXTAS is a genetic disorder, I will also be collecting molecular data to look for associations between these and the motor and cognitive measures.

I earned my BA in psychology from Washington University in St. Louis in 2010, after which I spent three years as a research assistant working on epidemiological studies at the Rush Alzheimer Disease Center (RADC). My work at the RADC included neuropsychological and motor testing, which sparked my interest in pursuing movement disorders research in my doctoral studies, which I began in the Fall of 2013.

Dr. O’Keefe’s collaboration with Drs. Deborah Hall and Elizabeth Berry-Kravis in Rush’s Department of Neurology has allowed me to work with the most cutting-edge technologies and given me access to patients from one of the largest movement disorders clinics in the country, allowing me to conduct top-of-the-line clinical research.

Nicollette Purcell

I am a graduate student in the Department of Cell & Molecular Medicine, working with Joan O’Keefe on my master’s thesis. My research is focused on patients with Huntington’s disease (HD), a movement disorder that impairs functional abilities, including gait and cognition. I will be measuring gait variables and cognitive function domains under single and dual-task conditions in individuals who are in the early stages of disease progression. Subjects will then be compared to age-matched controls to determine how HD quantitatively affects gait and cognitive function performance.

I received a BS in human biology from Michigan State University in 2013, and a BMS in pre-medical studies from Dominican University in 2014. Since then, I have been working as a certified nursing assistant caring for patients with HD and amyotrophic lateral sclerosis, and this experience has inspired me to pursue my graduate degree at Rush. It is my privilege to have the opportunity to work with Dr. O’Keefe, in collaboration with Dr. Jennifer Goldman, MD, at one of the nation’s best movement disorder centers.

Contact

Joan A. O’Keefe, PhD, PT
Associate Professor
Department of Cell & Molecular Medicine
Rush Medical College
Email: joan_a_okeefe@rush.edu