Stefan Feske, MD, NYU School of Medicine (Organizer)

NYU Langone Medical Center, Smilow Research Building, 1st floor seminar room
December 3rd, 2018

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Lecture Line Up

7:30-8:30am

7:30-8:30am

BREAKFAST / COFFEE
8:30-8:45am

8:30-8:45am

WELCOME & INTRODUCTION

Stefan Feske, New York University
8:45-10:30am

8:45-10:30am

SESSION 1: Regulation of immune cell development and function by ion channels

Chair: Bimal Desai, University of Virginia
 
Michael D. Cahalan, PhD

Calcium, calcium, calcium: Orai1 function and new probes for optical recording in T cells

Michael Cahalan, University of California, Irvine

We have developed new genetically encoded tandem reporters to optically record Orai1 channel activity at the single-molecule level and in the complex tissue environment of T cells migrating in lymph nodes. In this talk, Dr. Cahalan will discuss development and implementation of Salsa6f, a ratiometric green/red indicator to monitor cytosolic calcium signals; and Orai1-GCaMP6f, a channel-indicator to monitor calcium in the cytosolic nanodomain adjacent to Orai1 channels. Topics will include: molecular steps of Orai1 channel gating, variations in Orai1 kinetics and local signalling in puncta, and links between Orai1 channel activity and T cell motility.


 Michael D. Cahalan, PhD
 
Bimal N. Desai, PhD

The function of TRPM7 channels in innate immunity

Bimal Desai, University of Virginia

The talk will discuss the role of ion channels in regulating the crosstalk between macrophages and other cell types. The findings are focused on the role of ion channel TRPM7.


 Bimal N. Desai, PhD
 
Janet Chou, MD

The contribution of LRRC8A, an essential component of the volume-regulated anion channel, to mature T cell function

Janet Chou, Harvard Medical School

Leucine-Rich Repeat Containing 8A (LRRC8A) is essential for the development of T and B cells. This talk focuses on the role of LRRC8A as a costimulatory receptor for mature T cell activation and its therapeutic implications.



 Janet Chou, MD
 
Daniela Buccella, PhD

Illuminating Metals: Fluorescent Probes for the Study of Cellular Ion Homeostasis

Daniela Buccella, New York University (Short Talk)

The talk will focus on the development of fluorescent probes for the study of ion trafficking at the cellular levels, and their application in the study of Mg2+ transport and its influence in Ca2+ mobilization.


 Daniela Buccella, PhD
10:30-11:00am

10:30-11:00am

COFFEE BREAK
11:00am-12:45pm

11:00am-12:45pm

SESSION 2. Ion channels in immunity and inflammation

Chair: Stefan Feske, New York University
 
Michael Lenardo, MD

Critical role of Mg2+ in T cell activation and proliferation

Michael Lenardo, National Institute of Allergy and Infectious Diseases, NIH

Current estimates are that the typical American diet is deficient for magnesium intake. We find that insufficient Mg2+ causes defects in T cell function in vitro and a poor immune response against influenza virus infection. In this talk, Dr. Lenardo will describe the effects of magnesium deficiency on T cell activation and immune function.

 Michael Lenardo, MD
 
Susan R. Schwab, PhD

Exit strategies: S1P gradients and T cell migration

Susan Schwab, New York University

In this talk, Dr. Schwab will discuss the potential of modifying sphingosine 1-phosphate signaling to treat inflammatory disease, with a focus on the sphingosine 1-phosphate transporter SPNS2.

 Susan R. Schwab, PhD
 
Stephen Jameson, PhD

Regulation of T cell memory by the P2RX7 ion channel

Stephen Jameson, University of Minnesota

Activation of the purinergic receptor P2RX7 by extracellular ATP promotes innate immune activation, but its role in regulating adaptive immune cells is less clear. In this talk, Dr. Jameson will discuss that P2RX7 is required to generate and maintain long-lived memory CD8+ T cells, and that P2RX7 activation promotes mitochondrial function and metabolic fitness in 'central' and 'resident' memory subsets. As a result, treatment with P2RX7 inhibitors – used to control chronic neuropathic pain – leads to loss of protective memory CD8+ T cells. In this talk Dr. Jameson will summarize these findings and discuss them in the context of P2RX7 as an ion channel.


 Stephen Jameson, PhD
 
Stefan Feske, MD

CRAC channels in immunity to infection and autoimmunity

Stefan Feske, New York University

CRAC channels encoded by ORAI and STIM proteins are essential for T cell function in immunity to infection, but they also regulate immune homeostasis by regulatory T cells and promote inflammation by Th1 and Th17 cells. In this presentation, Dr. Feske will discuss the signaling pathways controlled by CRAC channels and how they regulate T cell function in the context of immunity to infection and in autoimmunity.

Stefan Feske, MD
12:45-1:30pm

12:45-1:30pm

LUNCH BREAK
1:30-2:45pm

1:30-2:30pm

POSTERS
2:45-4:30pm

2:30-4:30pm

SESSION 3. Ion channels in cancer

Chair: Kevin Foskett, University of Pennsylvania
 
J. Kevin Foskett, PhD

Ca2+ addiction of cancer cells

Kevin Foskett, University of Pennsylvania

Interruption of endoplasmic reticulum-to-mitochondria transfer of calcium causes a bioenergetic crisis in normal cells as well as in cancer cells. Whereas both normal and tumorigenic cells activated autophagy as a pro-survival mechanism, in cancer cells this is insufficient and they die, seemingly by mitotic catastrophe. In this talk, Dr. Foskett will discuss the basis for the reliance of cell metabolism on this calcium transfer and discuss why cancer cells may be particularly susceptible when it is interrupted.


 J. Kevin Foskett, PhD
 
George Miller, MD

Ion channels in innate and adaptive immunity to pancreatic ductal adenocarcinoma

George Miller, NYULH, USA

We investigated the role of select ion channels in regulation of T cell activation and myeloid cell recruitment to the tumor microenvironment and in viral and bacterial sepsis. In this talk, Dr. Miller will discuss how interruption of specific ion channel signaling in these cells can lead to protective immunity in infectious and neoplasic diseases.

George Miller, MD
 
Laura Conforti, PhD

KCa3.1 channel activity and CD8+ T cell function in the tumor microenvironment

Laura Conforti, University of Cincinnati

The tumor microenvironment limits the ability of T lymphocytes to infiltrate the tumor mass and kill cancer cells. These immunosuppressive effects of the tumor microenvironment occur through the inhibition of potassium channels in T lymphocytes. Potassium channels are thus potential targets for immunotherapy in cancer as their activation could restore the functionality of tumor infiltrating T lymphocytes. In this talk, Dr. Conforti will provide evidence of a role for potassium channels in mediating the effects of the hypoxic and adenosine-rich tumor microenvironment in head and neck cancer.


 Laura Conforti, PhD
 
Minsoo Kim, PhD

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Minsoo Kim, University of Rochester

Tumor microenvironments employ several strategies to attenuate effective immune-mediated tumor killing by interfering with nearly every step required for the host immunity, including prevention of immune cell homing to the tumor sites and suppression of the anti-tumor functions by generating strong immunosuppressive environments. Recently, adoptive cell transfer utilizing genetically engineered cytotoxic T lymphocytes (CTLs) (e.g., chimeric antigen receptor (CAR)-T cells) has emerged as one of the effective immunotherapeutic options against hematological malignancies, but significant clinical success has not yet been achieved for solid tumors. The goal of our research is to develop new “optogenetic” approaches to define the checkpoints and identify molecular interactions that can guide successful cancer immunity at the tumor sites. In this talk, Dr. Kim will discuss novel optogenetic approaches that can control (a) T cell recruitment (chemokine signal), (b) T cell activation (Ca++ regulation), and (c) off-target cytotoxicity of T cells using light stimulation.

 Minsoo Kim, PhD
4:30-4:45pm

4:30-4:45pm

COFFEE BREAK
4:45-6:30pm

4:45-6:30pm

SESSION 4: Ion channels as drug targets for immunotherapy

Chair: Michael Lenardo, NIH
 
Christine Beeton, PhD

Targeting potassium channels in rheumatoid arthritis

Christine Beeton, Baylor College of Medicine

Fibroblast-like synoviocytes (FLS) upregulate KCa1.1 (BK) channels and become highly invasive and erosive during rheumatoid arthritis (RA). Blocking KCa1.1 inhibits their invasiveness and attenuates disease severity in animal models of RA. Combining blockers of KCa1.1 and of Kv1.3 channels on effector-memory T lymphocytes is synergistic in animal models of RA. In this talk, Dr. Beeton will discuss our latest published and unpublished data supporting the targeting of potassium channels for the treatment of rheumatoid arthritis.


 Christine Beeton, PhD
 
Edward Skolnik, MD

Phosphoregulation of K+ channels in T cells

Edward Skolnik, New York University

In this talk, Dr. Skolnik will discuss the role of histidine phosphorylation/dephosphorylation in T lymphocyte activation via the regulation of the potassium channel KCa3.1 and the potential to target this pathway to inhibit T cell activation in autoimmune disease or to enhance activation to promote tumor killing.

 Edward Skolnik, MD
 
Anant Parekh, PhD

CRAC channels: drug targets in allergy and airway inflammation

Anant Parekh, University of Oxford, UK

In this talk, Dr. Parekh will discuss the involvement of store-operated calcium channels in mast cell activation by house dust mite and other allergens both in vitro and in a mouse model of asthma.

 Anant Parekh, PhD
 
Kenneth A. Stauderman, PhD

CRAC Channels as Targets for Drug Discovery and Development

Ken Stauderman, Calcimedica, La Jolla

CRAC channels have long been considered plausible drug targets. In this talk, Dr. Stauderman will discuss the challenges associated with CRAC channel drug discovery and development, including target selection, descriptions of pharmacological, safety and toxicological profiles of compounds, and finally clinical trials for CRAC channel inhibitors. Data on CM2489, the first CRAC channel inhibitor to enter clinical trials, will be presented, as well as data on other compounds currently in preclinical or clinical development.

 Kenneth A. Stauderman, PhD
6:30-7:30pm

6:30-7:15pm

RECEPTION
8:00-11:00pm

7:30-9:30pm

SPEAKER DINNER