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Pharmacology & Chemical Biology Seminar Series
9/15/2022 - 12:00 PM-1:00 PM
"The Novel Treatment of Engineered hACE-2 Decoy Peptide to SARS-CoV-2 & Its Variants-Induced Acute Lung Injury"  

Lianghui (Lucy) Zhang, M.D., Ph.D. 
Assistant Professor of Medicine 
Division of Pulmonary, Allergy, Critical Care Medicine 
Vascular Medicine Institute 
University of Pittsburgh School of Medicine  

“Continuing emergence of SARS-CoV-2 variants of concern that may escape vaccine-induced immune responses highlight the urgent need for effective COVID-19 therapeutics. We identified an engineered soluble ACE2 protein (sACE22.v2.4-IgG1), which markedly augmented the affinity for the S protein of the SARS-CoV-2 multiple variants of concern (VOCs): B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (omicron). We demonstrated prophylactic and therapeutic injections of sACE22.v2.4-IgG1 prevented lung vascular injury and edema formation induced by SARS-CoV-2 VOCs including omicron. Furthermore, we found that the catalytic activity of the decoy receptor is required for its therapeutic efficacy to increase survival of SARS-CoV-2 infected K18-hACE2 transgenic mice."
 

Pharmacology & Chemical Biology Seminar Series
9/22/2022 - 12:00 PM-1:00 PM
"EROS: controlling the phagocyte respiratory burst and purinergic signaling"

 

Dr David Thomas MA MB BChir PhD MRCP (Neph) 
Reader in Immunity and Inflammation and Honorary, Consultant Nephrologist
Wellcome-Beit Clinical Research Career Dev Fellow, Imperial College London

I will outline our characterisation of EROS (CYBC1 gene), a hitherto undescribed protein that acts as a super-selective chaperone for the gp91phox subunit of the phagocyte NADPH oxidase as well as the ATP receptor P2X7. EROS-deficiency in both mouse and human causes a severe immunodeficiency. The talk will focus on its discovery, role in immune physiology and molecular mechanism of action.

 

Pharmacology & Chemical Biology Seminar Series
9/29/2022 - 12:00 PM-1:00 PM
“The cell biology of heme trafficking and a new role for NO in its regulation”
 

Dennis Stuehr, PhD 
Professor, Cleveland Clinic, Lerner Research Institute

Heme is an important form of biologically active iron in cells. Heme levels participate in cell signaling and gene expression, and when bound in proteins enables various electron transfer, small molecule transport, and catalytic functions.  Because the final steps of heme biosynthesis take place inside the mitochondria and free heme is toxic, mechanisms exist to carefully control its level and to enable its transport and delivery to the many hemeproteins that mature and function outside of the mitochondria.  Moreover, evidence is emerging to suggest that differences in heme allocation and homeostasis influence important aspects of cancer progression and inflammation. Our lab is identifying the proteins that help to deliver heme and insert it into proteins, and uncovering the mechanisms that regulate these processes. The talk will highlight key roles for GAPDH and chaperone hsp90 in driving heme delivery and insertion into various targets including sGC, hemoglobin, myoglobin, NOS, and Trp dioxygenases, and will show how biologic NO can either up- or down-regulate these processes, depending on its flux. Overall, these findings may help explain how heme homeostasis is achieved in cells and can become dysregulated in disease.
 
 

Pharmacology & Chemical Biology Seminar Series
10/6/2022 - 12:00 PM-1:00 PM
“Mechanisms of beige adipocyte formation and maintenance”

Yuwei Jiang, PhD 
Assistant Professor
Department of Physiology and Biophysics
University of Illinois at Chicago

The induction of thermogenic beige adipocytes in white adipose tissue is a promising avenue for the treatment of obesity and Type 2 diabetes. In this seminar, I will discuss the cell origins of beige adipocytes, and then present a novel mechanism regulating beige adipocyte formation and maintenance that could be developed therapeutically.

 

Pharmacology & Chemical Biology Seminar Series
10/20/2022 - 12:00 PM-1:00 PM
“cAMP signaling at the nanometer scale”

Prof. Dr. Andreas Bock 
Medical Faculty
Leipzig University
Rudolf-Boehm-Institute of Pharmacology and Toxicology
 

G protein-coupled receptors (GPCRs) form the largest family of cell membrane receptors and modulate almost any (patho)physiological process in humans. GPCR signaling involves activation of distinct G-protein families, modulation of multiple intracellular second messengers, such as cAMP, and activation of kinases. Therefore, GPCRs orchestrate overwhelmingly complex intracellular signaling networks that are capable of precisely relaying signals in space and time to exert a myriad of specific cell functions. 
To ensure signaling specificity, GPCRs and their downstream signals are compartmentalized in very small regions in the cell that are called nanodomains. In my talk, I will introduce the concept of signaling compartmentation and highlight our recent work on cAMP nanodomains. Disruption of GPCR signaling networks can lead to noncommunicable diseases such as heart failure and cancer, and I will briefly discuss potential roles of nanodomain signaling in such diseases.  

 

Pharmacology & Chemical Biology Seminar Series
11/3/2022 - 12:00 PM-1:00 PM
“mTOR in brain development and disease”
 

Mustafa Sahin, MD, PhD  
Professor, Neurology
Harvard Medical School
 

Dr. Sahin will discuss the role of TSC1 and TSC2 proteins in regulating various neuronal functions through mTOR in cell culture and animal models and the implications of the basic research for developing therapies for clinical indications.
 

Pharmacology & Chemical Biology Seminar Series
11/10/2022 - 12:00 PM-1:00 PM
“Discovering new signaling pathways for the calcineurin phosphatase"
 

Martha Cyert, PhD 
Chair, Department of Biology
Stanford University

We are systematically discovering signaling pathways for Calcineurin, the calcium/calmodulin regulated phosphatase and target of immunosuppressants FK506 and Cyclosporin A. Using in silico and experimental approaches we are demonstrating new roles for calcineurin in Notch signaling, phosphoinositide signaling, at the nuclear pore and at centrosomes and cilia.
 

Pharmacology & Chemical Biology Seminar Series
12/1/2022 - 12:00 PM-1:00 PM
“Interplay of chromatin remodelling and nuclear receptor networks in breast cancers”
 

Sankari Nagarajan, PhD  
Lecturer in Chromatin Biology
University of Manchester
 


Pharmacology & Chemical Biology Seminar Series
12/8/2022 - 12:00 PM-1:00 PM
“Structural basis of LRRK2 activation – a molecular paradigm of kinase spatial regulation”

Ji Sun, PhD 
Assistant Member
St. Jude Children’s Research Hospital

Gain-of-function mutations in LRRK2 lead to Parkinson’s Disease (PD); therefore, LRRK2 inhibitors hold great potential for PD treatment. In this seminar, Dr. Sun will discuss the structure-function relationship of LRRK2, focusing on the following questions. 1) What is the architecture of LRRK2, a 286-kDa multi-domain protein? 2)  How is LRRK2 recruited to membrane surface by Rab GTPase? 3) How is LRRK2 activated upon membrane recruitment. And 4) What can we learn about LRRK2 PD mutations to guide future drug development?  
 

Pharmacology & Chemical Biology Seminar Series
12/15/2022 - 12:00 PM-1:00 PM
“The secret life of G proteins”

Mikel Garcia-Marcos, PhD 
Professor
Department of Biochemistry
Boston University School of Medicine
 

Our research program aims to understand the mechanisms and consequences cell communication via heterotrimeric G-proteins (Gαβγ) because they represent major intracellular hubs of signaling with very direct biomedical relevance. To achieve this goal, we use a wide range of approaches (biochemistry, cell biology, genetics, drug screening/ development) and experimental systems (purified proteins, cultured cells, model organisms) in combination with the development of novel tools (biosensors, chemogenetics, optogenetics). Our ongoing efforts have direct implications in cancer, embryonic development defects, and neurological disorders.

 
 
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