faculty photo

Robert Gordon Kalb

Professor of Neurology
Department: Neurology
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
Abramson Research Center #814
3615 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215 590 0691
Fax: 267 426 5165
Education:
B.A. (Biology)
Wesleyan University , 1978.
MD (Medicine)
Cornell University Medical College, 1982.
Post-Graduate Training
Intern in Medicine, Montefiore Hospital, Bronx, NY, 1982-1983.
Resident in Medicine, Montefiore Hospital, Bronx, NY, 1983-1984.
Resident in Neurology, Yale-New Haven Hospital, 1984-1987.
Postdoctoral Fellow, Department of Neurobiology, Yale University, New Haven, CT, 1987-1990.
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Description of Clinical Expertise

I am a Board Certified Adult Neurologist who has been in active and continuous practice since 1987. I have facility in the treatment of a broad range of Neurological Disorders. I have special expertise in the diagnosis and management of ALS patients.

Description of Research Expertise

Research in my lab focuses on two topics: 1) activity-dependent development of circuits in the central nervous system and 2) healthful compensatory responses of cells and organisms to stressful conditions. We use genetically manipulated mice, primary neuron tissue culture and C.elegans in our studies; our approach is cell and molecular biology.
During development synaptic activity refines and patterns connections among neurons and this is required for precise high-level behavior. We have found that glutamatergic synapses that include the GluA1 subunit have a privileged role in this process likely a function of specific electrophysiological properties and through the assembly of a large multi-protein complex in the sub-synaptic domain. A critical molecular component of this complex is SAP97, a scaffolding protein with >90 known binding partners. We have taken a variety of approaches to identifying the critical binding partners of SAP97 that transduce activity of glutamate receptors assembled with GluA1 into dendrite growth, synapse specification and circuit function. Insight in the molecular logic of SAP97 function will have implications for childhood maladies such as intellectual disability and autism/autism-spectrum disorders.
Mutations in protein such as Cu++/Zn++ SOD and TDP43 cause adult onset neurodegenerative diseases such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. We have found that these mutant proteins evoke maladaptive changes in cellular and organismal intermediary metabolism – re-wiring metabolism can blunt the adverse effects on neuronal survival. We have made parallel observations in an infantile/childhood motor neuron disease called Spinomuscular atrophy. In addition, mutant protein misfolding can be injurious to neurons by disrupting cellular protein homeostasis and we have identified suppressors of this toxicity. Targeting proximal events in neurodegenerative diseases will lead to novel therapeutic approaches.

Selected Publications

Jablonski, A.M., Lamitina, T., Liachko, N.F., Sabatella, M., Liu, J., Zhang, L., Ostrow, L.W., Gupta, P., Wu, C.-Y., Doshi, S., Mojsilovic-Petrovic, J., Lans, H., Wang, J., Brian C Kraemer, B.C., and Kalb, R.G: Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance. Journal of Neuroscience 2015.

Zhai, J.,Zhang, L., Mojsilovic-Petrovic, J., Jian, X., Thomas, J.,Homma, K., Schmitz, A., Famulok, M., Ichijo, H., Argon, Y., Randazzo, P.A. and Kalb, R. G: Inhibition of cytohesins protects against genetic models of motor neuron disease. Journal of Neuroscience 2015.

Boccitto, M., Doshi, S., Maronski, M., Zhai, J., Zhang, L. and Kalb, R.: Opposing Actions of SAP97 and DISC1 on Wnt/β-catenin Signaling. Neuroscience 2015.

White, S., Ortinski, P., Shayna H., Friedman, S.H., Neve,R. L., Kalb, R. G., Schmidt, H.D., and Pierce, R. C.: A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking. Neuropsychopharmacology 2015.

Zhang, L., Hsu,F.-C., Mojsilovic-Petrovic, J., Jablonski, A.M., Zhai, J., Coulter, D.A. and Kalb, R.G. : Structure-Function Analysis Of SAP97, A Modular Scaffolding Protein That Drives Dendrite Growth. Mol Cell Neuroscience 65, 2015.

Ozek, C., Zimmer, D.J., De Jonghe, B.C., Kalb, R.G., and Kendra K. Bence, K.K.: Ablation of intact hypothalamic and/or hindbrain TrkB signaling leads to perturbations in energy balance. Molecular Metabolism 2015.

Goran Periz, Jiayin Lu, Tao Zhang, Mark W. Kankel, Angela M. Jablonski, Robert Kalb, Alexander McCampbell, Jiou Wang : Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription Plos Biology 2015.

Alondra Schweizer Burguete Sandra Almeida Fen-Biao Gao Robert Kalb Michael R Akins Nancy M Bonini : GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function. eLife 2015.

Flibotte, J.J., Jablonski, A.M. and Kalb R.G.: Oxygen sensing neurons and neuropeptides regulate survival after abnoxia in developng C. elegans. PloS One 9, 2014.

Lim, M.A., Bence, K.K, Sandesara, I., Andreux, P., Auwerx, J., Ishibashi, J., Seale,P. and Kalb, R.G.: Genetically altering organismal metabolism by leptin-deficiency benefits a mouse model of amyotrophic lateral sclerosis. Human Molecular Genetics doi:10:1093/hmg/ddu214, 2014.

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Last updated: 09/12/2016
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