Free Coffee & Continental Breakfast Provided by Translational Research Conference
Welcome & Opening Remarks by Chris Mathes, Ph.D., Chief Commercial Officer at AnaBios
Keynote Lecture by Kalyanam Shivkumar, Ph.D., Professor of Medicine, Radiology & Bioengineering at the University of California–Los Angeles
“Advantages of Direct-in-Human Basic Research for Analgesic Drug Development,” presented by Mike Iadarola, Ph.D., Sr. Research Scientist at the National Institutes of Health
This presentation examines how transcriptomics and multiplex in situ hybridization informs the process of analgesic drug discovery, development, and prediction of side effects.
Presentation by Alpenglow Biosciences, Translational Research Conference Sponsor
“Modeling Human Liver Disease Using Bioengineered Tissues,” presented by Rob Schwartz, Ph.D., Assistant Professor of Medicine at Cornell University
Presentation by Eric Nisenbaum, Ph.D., Sr. Vice President at Grunenthal
Lunch Provided by Translational Research Conference
“Novel Drug Discovery in Precision Cardiology,” presented by Carla Klattenhoff, Ph.D., Senior Director of Preclinical Research at Bayer
Medical innovation and lifestyle improvements have resulted in significant therapeutics advances in cardiology. To continue to deliver breakthrough innovation with clear value propositions we must adapt our research strategy and focus on high medical need patient segments. Our transformation will be founded upon a deep understanding of patient subpopulations and their biological dysfunction with identification of the best modality to achieve a highly differentiated therapeutic benefit.
Presentation by Alcyomics, Translational Research Conference Sponsor
“Navigating A New Path to Nav1.7 for Pain,” presented by Rajesh Khanna, Ph.D., Director of New York University Pain Research Center
Pain remains a global health crisis. Despite extensive efforts by big pharma and academic labs worldwide, only opioids (new formulations of enhanced potency) have emerged clinically in the last few decades. While efficient for acute pain treatment, there is unanimous consensus that opioids are not recommended for treatment of long-term chronic pain. New, non-opioid, drugs are urgently needed. The NaV1.7 sodium channel is a prized target for pain therapeutics since mutations in the human gene, SCN9A, have been reported to produce both too much pain – due to gain-of-function mutations – or no pain – due to loss-of-function mutations. But despite these genetic links, development of NaV1.7 inhibitors has been unsuccessful due to reported lack of selectivity, insufficient channel blockade, and failure to engage NaV1.7-dependent endogenous opioid signaling. In this talk, Dr. Khanna will synthesize the history and discovery of this validated target, discuss the identification of NaV1.7 as a pharmacogenomic target, and illustrate the allosteric and gene therapy-based therapeutic potential of NaV1.7. He will also discuss how use of non-human primate-based assays may offer a hope for the future therapeutics targeting this channel.
Presentation by Najah Abi-Gerges, Ph.D., Vice President of Research & Development at AnaBios
Coffee Break Provided by Translational Research Conference
“Antibody Mediated Blockade of Interleukin-11 Signaling for IPF and Other Fibrotic Diseases,” presented by Jamie Swaney, Ph.D., Vice President of Fibrosis & Translational Biology at Lassen Therapeutics
Interleukin 11 (IL-11) is a pleiotropic cytokine that is increasingly being recognized for its role in fibroinflammatory biology. IL-11 binds to IL-11 receptor (IL-11Rα), and recruits gp130, promoting phosphorylation of STAT3 and ERK with subsequent effects on cellular proliferation, survival, migration/invasion, angiogenesis and differentiation. IL-11 also exhibits crosstalk with other fibroinflammatory mediators such as TGFβ, PDGF and CTGF. In this talk, Dr. Swaney will provide background on the role of IL11/IL11RA in lung fibrosis and other fibrotic diseases. Furthermore, he will discuss how Lassen Therapeutics has taken a multi-pronged translational biology approach of using primary cells/tissues, in vivo models and ex vivo translational assays such as precision cut lung slices, to interrogate the profibrotic effects of IL-11 and develop a first-in-class, clinical stage IL-11Rα blocking antibody, as a treatment for tissue fibrosis.
Presentation by Dinah Misner, Ph.D., Vice President of Aligos Therapeutics
Presentation by Cureline, Translational Research Conference Sponsor
“Development of Human Spinal Cord Assays for Investigating Mechanisms and Novel Treatments for Pain,” presented by Mike Hildebrand, Ph.D., Associate Professor at Carleton University
In this presentation, Dr. Hildebrand will highlight his recent work aimed at bridging the translational divide between rodent preclinical work on spinal pain processing and new treatment approaches for humans. His team has developed new human spinal cord tissue models of pain signaling that parallel rodent in vivo and ex vivo pain models. Using these complementary approaches, they are investigating molecular mechanisms of pain processing across development, sex and species, including the regulation of excitatory glutamate receptors and neuronal excitability in dorsal horn nociceptive circuits.
Cocktail Reception & Poster Presentation
Dinner at the Hilton La Jolla Torrey Pines, Provided by Translational Research Conference
TUESDAY, FEBRUARY 28, 2023
Opening Remarks & Recap of Day 1 by Chris Mathes, Ph.D., Chief Commercial Officer at AnaBios
“Molecular Profile of the Human Dorsal Root Horn,” presented by Keynote Speaker Ted Price, Ph.D., Associate Professor at University of Texas-Dallas
Dr. Price’s presentation will focus on defining the molecular profile of dorsal horn neurons using spatial and single cell RNA sequencing, proteomics and immunohistochemistry/RNAscope. His work is focused on understanding the first synapses in the pain pathway in humans, with an emphasis on projection neurons.
“Cardiac Tissue Slices to Model Cardiac Health and Disease in Culture,” presented by Tamer Mohamed, Ph.D., Associate Professor at the University of Louisville
There is an urgent need for a reliable in vitro system that can accurately replicate the cardiac physiological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Dr. Mohamed’s team had previously developed a culture system for pig/human heart slices that enables functional and structural viability for six days under electric stimulation and enriched media and can reliably demonstrate the subacute toxic effects of anti-cancer therapeutics. Most recently, his team developed a novel cardiac tissue culture model (CTCM) that can electro-mechanically stimulate heart slices with physiological preload and afterload during each cardiac cycle.
Presentation by Yurong Lai, Ph.D., FAAPS, Executive Director of Drug Metabolism, Gilead Sciences
Presentation by ACD, Translational Research Conference Sponsor
“Respiratory Drug Discovery Using Precision Cut Lung Slices” by Rama Krishnan, Ph.D., Associate Professor of Emergency Medicine at Harvard University
A powerful tool for studying lung (patho)physiology is the preparation of precision-cut lung slices (PCLS). In PCLS, airway and septal wall geometry can be readily visualized, while stiffness, mechanotransduction, and airway smooth muscle contraction precisely quantified. Neural stimulation and dynamic stretching can also be superimposed. PCLS can be prepared and cryopreserved from naïve, genetically modified, or diseased animals as well as from human surgical samples and lung explants. In this talk, Dr. Krishnan will describe how these unique advantages are enabling the identification of the next generation of respiratory medications.
Lunch Provided by Translational Research Conference
“Insight Into Novel Itch Pathways & Spontaneous Neuronal Activity by Targeting Interleukin-13 Receptor Alpha 1 (IL-13Rα1) with Eblasakimab” by Ferda Cevikbas, Ph.D., Head of Translational Sciences at Aslan
Dr. Cevikbas will present data that confirms prior results of eblasakimab dampening neuronal sensitization caused by IL-4 and IL-13 on human neurons. In addition, IL-13 sensitized hDRG neurons to pro-adrenomedullin peptide 1-20 (PAMP20), demonstrating that the itch-specific MRGPRX2 receptor is expressed and functional in human sensory neurons, suggesting an enhancer role of Type 2 cytokines in a wide variety of itch-associated diseases. IL-4 induced spontaneous activity (SA) in hDRG neurons under inflammatory conditions which may underly the mechanistic basis for altered neuronal sensitivity in inflammatory conditions. This data suggests that IL-13 and IL-4 may play distinct roles in affecting neuronal activity and eblasakimab was shown to block the effects of both cytokines.
“Impact of Oxytocin on Human Sensory Neurons,” presented by Dave Yeomans, Ph.D., Professor at Stanford University
For several years, Dr. Yeoman’s group has investigated the potential of intranasally applied oxytocin for the treatment of various head pain disorders, including migraine headache. This preclinical and clinical work has been driven by our findings in rat cellular and behavioral assays. However, to provide support for human experimentation, it was critical to provide evidence not only of the inhibition of human sensory neurons by oxytocin, but also the circumstances of that inhibitory efficacy. Thus, Dr. Yeoman’s team enlisted the help of Anabios to provide not only human sensory ganglia tissue, but also experimental expertise, including specialized tissue preparation and patch electrophysiology. Thus far, this work has yielded several findings key to translation of the phenomenon of oxytocin-induced craniofacial analgesia to human patients. First, a human trigeminal ganglia (TG) study demonstrated both that many if not most neurons in the TG possessed oxytocin receptor (OTR) immunoreactivity, that there is a strong co-expression of calcitonin gene related peptide (CGRP) in these cells and that rapid treatment after dissection with the inflammatory driver lipopolysaccharide dramatically increases the expression of both CGRP and OTR. These studies also allowed his team to observe that, in the presence of LPS driven inflammation, there was a robust expression of both p-ERK and C-Fos, both immediate early genes which demonstrate neuronal activation.
Presentation by Hina Chaudhry, Ph.D., Professor of Medicine at Icahn School of Medicine at Mount Sinai