Current Projects

Project 1: Development of Antigen Specific Therapeutics and Novel Therapeutic Approaches of Autoimmune Disorders

Prof. Stoddard pointing to a computer with a student
Photo credit Noah Stewart ‘22

Autoimmune disease affects at least 23.5 million Americans, and is the 2nd leading cause of long-term chronic illness. Autoimmune disease is caused when a person’s immune system begins to attack healthy cells in the body. Current therapies for autoimmune disease often utilize non-specific drugs that suppress the entire patient’s immune system. This approach increases the risk of patients contracting other infections more easily and decreases their ability to fight infections off successfully. Thus, the goal of our research is to develop more targeted therapeutic approaches that will only suppress the aberrant portion of a patient’s immune system. In this project we focus on engineering proteins that can inhibit the immune system from attacking healthy cells. The MIR lab currently focuses on developing therapeutics for primary membranous nephropathy and systemic lupus erythematosus.

Collaborators:

Laurence Beck, Jr.: Boston University Medical College
Roberto de la Salud Bea: Rhodes College
Kim Brien: Rhodes College
Gérard Lambeau: Institut de Pharmacologie Moléculaire et Cellulaire (France) 

Project 2: Modelling and Investigation of Structure and Function Relationships of Unsolved Protein Structures Involved in Autoimmune, Cancer, or Neurological Disease Pathogenesis

image of a protein structure

Understanding protein structures associated with autoimmune disorders, cancer, and neurological disorders is essential to developing better therapeutics. Many of the proteins of interest in these disorders are uncharacterized. Thus, my lab also focuses on developing 3D-models of protein structures related to cancer and protein antigens involved in autoimmune disorders. Recently, we successfully developed a homology model of the 250kDa thrombospondin type-1 containing domain 7A antigen involved in the autoimmune disorders idiopathic membranous nephropathy (IMN). Currently we are focused on using these models to understand the biological function of these proteins and in the design of therapeutic agents targeting them.

Collaborators:

Laurence Beck, Jr.: Boston University Medical College

Publications from this project:

Shana V. Stoddard, Colin L. Welsh, Maggie M. Palopoli, Serena D. Stoddard, Mounika P. Aramandla, Riya M. Patel, and Laurence H. Beck, Jr.Structure and Function Insights Garnered from In silico Modelling of the Thrombospondin Type-1 Domain-Containing 7A Antigen.  PROTEINS: Structure, Function, Bioinformatics.  Proteins. 2018 Dec 06. PMID: 3052053

Project 3: Design, Synthesis, and Biological Testing of Novel Compounds having Improved Performance as Cancer Therapeutics

a professor and student measuring a substance in the lab
Photo credit Noah Stewart ‘22

Cancer is the second leading cause of death in the United States.  In the MIR lab we develop compounds that could be used to treat several cancer types.  Our compound are designed to target a family of 18 enzymes called histone deacetylases (HDAC) that are important for gene regulation. It has been shown that different types of cancers vary in the amount and type of HDAC enzymes they express, making them good drug targets for cancer therapy. Unfortunately there have been challenges in designing HDAC inhibitors that can target only one specific HDAC enzyme out of the family of 18. Thus, this project focuses on development of not only potent HDAC inhibitors but also selective HDAC inhibitors. One of the specific cancers that the MIR lab targets is neuroblastoma which, has been shown to have over expression of HDAC8. Neuroblastoma is a childhood pediatric cancer, which has proved difficult to treat. Therefore, we are developing selective HDAC8 inhibitors.

Collaborators:

Davita Watkins: University of Mississippi
 

Publications from this project:

Shana V. Stoddard, Xavier A. May, Fatima Rivas, Kyra Dodson, Sajith Vijayan, Swetha Adhika, Kordarius Parker, Davita L. Watkins.  Design of Potent Panobinostat Histone Deacetylase Inhibitor Derivatives: Molecular Considerations for Enhanced Isozyme Selectivity between Histone Deacetylase 2 (HDAC2) and Histone Deacetylase 8 (HDAC8) Molecular Informatics 37 (2018) 1800080

 

 

 

Project 4: Design, Synthesis and Biological Testing of Novel Therapeutics for Neurological Disorders

a professor and student with pipettes
Photo credit Noah Stewart ‘22

Neurological disorder are also impacted by the histone deacetylase family of enzymes.  In particular histone deacetylase 4 (HDAC4) has been found to be a relevant target for Huntington’s disorder. Recently we have identified a series of novel HDAC4 inhibitor compounds and produced guidelines for better HDAC4-selective inhibitors. Currently this project is focused on synthesis and biological testing of these compounds. These HDAC4-selective inhibitors would be ideal for the neurological disorder Huntington’s disease.

Collaborators:

Davita Watkins: University of Mississippi
Roberto de la Salud Bea: Rhodes College