Jonathan Soboloff, Ph.D.

Professional Background

Dr. Soboloff's laboratory is focused on understanding fundamental mechanisms regulating the generation of Ca²⁺ signals and the conversion of those signals into physiological and pathophysiological signals. Dr. Soboloff started working on Ca²⁺ signaling in ovarian follicular development in graduate school in the laboratory of Benjamin K Tsang under the supervision of Michel Désilets at the University of Ottawa. Dr. Soboloff then moved to the University of Toronto when he shifted his work to immunology, focusing primarily on targeting Ca²⁺ signals for the treatment of leukemia and mast cell-mediated inflammatory disease. He then moved to the University of Maryland where, working with Dr. Donald L. Gill, he investigated fundamental mechanisms of store-operated Ca²⁺ entry.

In 2007, Dr. Soboloff joined Temple University, where he published dozens of articles, primarily on STIM and Orai. Areas of focus include immunology, cancer and bone physiology. Dr. Soboloff's work has primarily been funded by the NIH, which currently supports his work.

• BSc, Pre-Health Professions Option, University of Waterloo, Waterloo, ON
• PhD, Physiology, University of Ottawa, Ottawa, ON
• Post Doctoral Fellowship, Immunology, University of Toronto, Toronto, ON
• Post Doctoral Fellowship, Pathobiology, University of Toronto, Toronto, ON
• Post Doctoral Fellowship, Biochemistry, University of Maryland, Baltimore, MD

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Research

Overview

The Physiology of Ca²⁺ Signaling
The overall focus of the lab is to characterize Ca²⁺ signaling mechanisms and define their physiological and pathophysiological roles. We are particularly interested in the STIM/Orai Ca²⁺ signaling system. STIM is an ER Ca²⁺ sensor that responds to loss of ER Ca²⁺ content by moving towards the PM where it activates the Orai Ca²⁺ channel, leading to the influx of Ca²⁺ across the PM. While this is the basic mechanism, we and others have revealed the existence of multiple mechanisms of STIM activation, numerous adaptor proteins and STIM targets, leading to a decidedly more complex relationship than originally believed.

Novel Ca²⁺-dependent control of T cell activation – Although STIM/Orai-dependent Ca²⁺ signaling is ubiquitous, immune cells exhibit a unique dependence on this Ca²⁺ signaling system due to their small size, lack of excitability and the ability of this signaling system to facilitate long-term signaling. Due to the nature of ion movement, sustaining Ca²⁺ signals over extended time periods requires unique mechanisms. Our lab has pubilshed numerous articles on this topic and it remains one of our interests.

Control of Orai1 activity in Invasive Melanoma – Somewhat counter-intuitively, we have found that Orai1 activity is inhibited in invasive melanoma through multiple mechanisms. Our effort to characterize the underlying mechanisms of this unusual observations have led us to consider metabolic reprogramming and the mediatory role of O-GlcNAcylation in this process. We are currently looking for a student interested in working on this project.

Control of bone density by Orai1 activity – Working in association with Exesalibero Pharma LLC, we have revealed critical roles for Ca²⁺ signals in the formation of osteoclasts (bone removal). Interestingly, while initial investigations focused on the role of Orai1 in osteoclastogenesis, our recent study of arthritis-induced bone erosion revealed an unexpected role for TRPC channels in pathological ostecolastogenesis. We are currently looking for a postdoctoral fellow interested in developing this project.

Defining the contribution of Orai1 to cystic fibrosis – Working closely with Dr. Tarran, we are interested in understanding the role of Orai1 in the development of disease in cystic fibrosis. Although lung fibrosis is the primary abnormality found within this disease, CF patients suffer from immunological abnormalities, altered rates of cancer development and osteoporosis. Future investigations will focus on the impact of CFTR mutations on Orai1 function and defining their relative roles in the development of CF-associated abnormalities.

• Targeting anoctamin 6 to disrupt the trogocytosis functions of cancer-associated fibroblasts, NIH-NCI, Co-PI

• Soboloff, Jonathan, Rothberg, Brad., S., Madesh, Muniswamy, Gill, Donald., L.. 2012. STIM proteins: dynamic calcium signal transducers. Nature Reviews Molecular Cell Biology, 13 (9), 549-565. https://doi.org/10.1038/nrm3414
• Ritchie, Michael., F, Samakai, Elsie, Soboloff, Jonathan. 2012. STIM1 is required for attenuation of PMCA-mediated Ca²⁺clearance during T-cell activation. The EMBO Journal, 31 (5), 1123-1133. https://doi.org/10.1038/emboj.2011.495
• Gross, S, Hooper, R, Tomar, D, Armstead, A., P, Shanas, N, Mallu, P, Joshi, H, Ray, S, Chong, P., L, Astsaturov, I, Farma, J., M, Cai, K., Q, Chitrala, K., N, Elrod, J., W, Zaidi, M., R, Soboloff, J. 2022. Suppression of Ca(2+) signaling enhances melanoma progression.. The EMBO journal, 41 (19), e110046
• Ray, S, McCall, J., L, Tian, J., B, Jeon, J, Douglas, A, Tyler, K, Liu, S, Berry, K, Nicewarner, B, Hall, C, Groschner, K, Bacsa, B, Geldenhuys, W, Zhu, M., X, Blair, H., C, Barnett, J., B, Soboloff, J. 2025. Targeting TRPC channels for control of arthritis-induced bone erosion.. Science advances, 11 (3), eabm9843