Mastering Metabolism

Metabolism is the sum of the chemical reactions that take place within each cell of a living organism. It is the fundamental process of converting food into energy, creating the building blocks of life—proteins, lipids, nucleic acids and more—and ensuring that the organism thrives.

Metabolic dysfunction disrupts this universal commonality of life and can lead to a broad spectrum of devastating, chronic diseases. At the center of metabolic functioning is the liver, which makes it at particular risk. Dysfunction in the body’s largest internal organ can create a cascade of harm.

Disease and the Immune Response

Pathogenesis—literally how disease (pathos) begins (genesis) or develops—is a broad and important area of research.

Many diseases can arise from pathogens, but the immune system protects us through various lines of defense. If the immune system fails to function properly and becomes too weak or too strong, it can lead to disease states that include immunodeficiencies that lead to enhanced susceptibly to infections disease, autoimmune conditions, such as lupus and arthritis, and even cancer. 

Harrows of Heredity

Most genetic disorders are present from birth. Fortunately, they are also exceedingly rare, perhaps affecting only one person in every several thousand or million.

Some are well known, such as sickle cell anemia and cystic fibrosis, but others are so infrequently seen or documented by clinicians that there may only be a handful of known cases in the world or in history. 

Whether a genetic disease afflicts thousands or a single person, it poses distinct and daunting  challenges for patients, their families and caregivers, not least that the average time it takes for most patients with a rare disease to get a correct diagnosis is nine years. We strive to shorten that diagnostic journey and point toward potential treatments.

Drug Discovery

Our mission is to expand and expedite the discovery and development of new cancer therapeutic agents based on novel insights into cancer biology.

We focus on the early stages of the drug discovery process, from target validation through “proof-of concept” studies, which seek to demonstrate that a newly discovered drug candidate can successfully alter the course of cancer disease progression. 

We combine the strengths and resources of faculty with complementary expertise in assay development, high-throughput screening, downstream medicinal chemistry and pharmacology through our partnership with the Conrad Prebys Center for Chemical Genomics.

Perilous Proteins

Proteins are the workhorses of the cell. They are required for the structure, function and regulation of the body’s tissues and organs. What they do and how well they do it depends upon their three-dimensional shape, which determines whether a protein can interact with other molecules.

When proteins are misfolded or damaged, they cannot perform their duties. Faulty proteins must be eliminated before they can accumulate, clump or become toxic. Although there are intrinsic cell mechanisms that recognize defective proteins and attempt to remove them, these systems can go awry or fail as we age. Almost every age-related degenerative disease is linked to protein misfolding.

Malignant Machinery

Like any complex machine comprised of multifarious but highly synchronized parts, cancer is the creation of diverse but organized cells and molecules driven by disinformation and dysfunction to produce malignant tissues and tumors.

Our program focuses on determining how nutrients and the microenvironment surrounding tumors interact to direct the formation, growth and spread of cancer cells. From individual metabolites to stromal cells, such as fibroblasts and immune cells, our goal is to discern the basic workings of tumors that cause disease, revealing a more comprehensive view of cancer biology that can be a guide to new therapies.

Biology of Becoming

Development, growth and aging are all directed or controlled by constant cues and signals from inside and outside the body, influenced by factors like injury, infection, stress and even what we eat. 

To adjust and adapt to these cues, cells send and receive signals through biological pathways. Our research investigates the codes, signals and cell changes associated with normal development and aging, seeking to distinguish them from those cues and signals linked to disease and disability. By translating this critical, constant chatter of life, we hope to create and speak a new vocabulary for improved health. 

Controlling Cancer

All cancers depend upon dysregulation and dysfunction of normal cell processes. These processes are often controlled by the cell nucleus, specifically by DNA sequence (the genome) and its regulation (the epigenome).

Dysregulation of nuclear processes encoded within the genome and/or epigenome drive many of the detrimental properties of cancer cells, such as defective DNA repair and mutation accumulation, altered inflammatory signaling and immune regulation, unrestrained cell growth and survival, tissue invasion, metastasis and drug resistance. Understanding these processes, including their dysregulation in aging and differences between races and ethnicities, can lead to new approaches for patient- and population-specific risk assessment, early detection and diagnoses of cancer, as well as novel therapeutic interventions.