Cancer & Microbes Working Group

The Cancer and Microbes Working Group is a new partnership between the Cancer Center at Illinois and the Microbial Systems Initiative to promote enhanced collaboration at the interface of microbial sciences and cancer. The “Cancer and Microbes” strategic initiative will be a part of the CCIL Cancer Discovery Platforms Bridging the Engineering-Biology Continuum (CDP) Program.

Vision

To connect researchers from diverse backgrounds to initiate unique collaborative relationships and generate data in the area of Cancer and Microbes.

Cancer and Microbes Working Group Meeting

Working Group Co-Leads

Sayeepriyadarshini (Sayee) Anakk

Sayeepriyadarshini (Sayee) Anakk

Associate Professor, Molecular and Integrative Physiology
anakk@illinois.edu

Shannon Sirk

Shannon Sirk

Assistant Professor, Bioengineering
sirk@illinois.edu

Directory

Jacob Allen

Jacob Allen

Assistant Professor, Kinesiology and Community Health
jmallen5@illinois.edu

Christopher Gaulke

Christopher Gaulke

Assistant Professor, Pathobiology
cgaulke@illinois.edu

Mohammed El-Kebir

Mohammed El-Kebir

Assistant Professor, Computer Science
melkebir@illinois.edu

H. Rex Gaskins

H. Rex Gaskins

Professor, Animal Sciences
hgaskins@illinois.edu

Brett Loman

Brett Loman

Assistant Professor, Animal Sciences
bloman2@illinois.edu

Joseph Irudayaraj

Joseph Irudayaraj

Professor, Bioengineering
jirudaya@illinois.edu

Collin Kieffer

Collin Kieffer

Assistant Professor, Microbiology
collink@illinois.edu

Erik Nelson

Erik Nelson

Associate Professor, Molecular and Integrative Physiology
enels@illinois.edu

Zeynep Madak-Erdogan

Zeynep Madak-Erdogan

Associate Professor, Food Science & Human Nutrition
zmadake2@illinois.edu

Sergei Maslov

Sergei Maslov

Professor, Bioengineering
maslov@illinois.edu

François Reichardt

François Reichardt

Research Scientist, Molecular and Integrative Physiology
fr7@illinois.edu

Jason Ridlon

Jason Ridlon

Associate Professor, Animal Sciences
jmridlon@illinois.edu

Taher Saif

Taher Saif

Professor, Mechanical Science and Engineering
saif@illinois.edu

Michael Spinella

Michael Spinella

Professor, Comparative Biosciences
spinella@illinois.edu

Beth Stadtmueller

Beth Stadtmueller

Assistant Professor, Biochemistry
bethms@illinois.edu

Shulei Wang

Shulei Wang

Assistant Professor, Statistics
shuleiw@illinois.edu

Bo Wang

Bo Wang

Assistant Professor, Comparative Biosciences
bowang@illinois.edu

Member Resources

Upcoming Events

Cancer and Microbes Seminar Series | May 2, 12 - 1 p.m.

Presenter:  Lyndsey Ly | Graduate student, Division of Nutritional Sciences

Brief description: The gut microbiome generates steroid metabolites that act as hormones, affecting not only local physiology, but also having systemic consequences if absorbed into circulation. One microbial pathway of emerging interest is the steroid-17,20-desmolase (DesAB) pathway that converts cortisol, a C21 glucocorticoid (GC), to 11b-hydroxyandrostenedione (11b-OHAD), a C19 pro-androgen. This is of clinical significance because 11b-OHAD is a precursor to 11-oxy-androgens, a class of androgens with potent androgenic activity, which can be generated by both host and resident microbes. In this work, the number of substrates for DesAB were expanded to also include pharmaceutical analogs of cortisol using both purified recombinantly expressed DesAB (rDesAB) and whole cells from two microbes from gut and urinary tract, Clostridium scindens ATCC 35704 and Propionimicrobium lymphophilum ACS-093-V-SCH5, respectively. In vitro culturing of androgen-responsive prostate cancer cells (LNCaP) showed that 1,4-androstadiene-3,11,17-trione, the product of bacterial side-chain cleavage of prednisone, caused significant proliferation relative to vehicle at 24 and 72 hours. We hypothesize that urinary microbes inhabiting a minimal nutrient environment metabolize GCs for energy, generating androgens that diffuse into surrounding prostate tissue, which may lead to increased proliferation of androgen-dependent prostate cancer cells. To better understand the physiological function of DesAB, the in vitro cortisol-induced transcriptome of a desAB-encoding gut microbe, Butyricicoccus desmolans ATCC 43058, was analyzed using RNA-Seq. Understanding bacterial androgen production is particularly important when assessing risk and progression in diseases that are exacerbated by high androgen levels, such as prostate cancer or polycystic ovary syndrome. Basic understanding of why and how the microbes are responding to cortisol, will lead to rational modulation of the extracellular environment to shift metabolism away from side-chain cleavage of GCs, which may have translating applications for human dietary interventions if DesAB is indeed contributing to disease.

 

Expanding the therapeutic capacity of engineered antibody fragments
Presenter:  Vince Kelly | Graduate student, Bioengineering

Brief description: One of the great challenges in the development of biotherapeutics to treat cancer is the high cost associated with these drugs, both in terms of manufacturing cost and the patient’s cost for treatment. Dosing regimens requiring repeated administration, trips to a healthcare provider, and large amounts of formulated therapeutic, are a significant driver of these costs. The goal of our research is to leverage the inherent capabilities of the diverse microbial community of the human gut to reduce these costs by acting as therapeutic factories in situ. Recent developments in microbial genetics, synthetic biology, and the study of niche-optimized, non-pathogenic members of the human gut microbiota have paved the way for the engineering of commensal bacteria to carry out novel functions. Using species-specific genetic components, therapeutic production can be achieved in both transiently and persistently colonizing members of the gut microbiota. While these engineered strains can be used to treat conditions localized to the gastrointestinal tract, we are currently utilizing a protein engineering approach to expand the potential applications of engineered microbes to systemic conditions. We have fused small (15 amino acid) peptides that mimic the neonatal Fc receptor (FcRn)-binding epitopes of IgG and albumin to single-chain Fv (scFv) antibody fragments. These modifications enable pH-dependent FcRn engagement and FcRn-mediated salvage or transport across polarized epithelial cell barriers, functionally mimicking the native FcRn-mediated half-life extension and transport of IgG and albumin. This work demonstrates the potential utility of peptide-modified scFvs either as purified therapeutics or as part of an in situ delivery system. Additionally, we are now engineering similar peptide-scFv fusions to engage immune-activating receptors CD16 and CD64 to improve the anti-cancer efficacy of engineered scFvs and are simultaneously exploring microbial and non-microbial non-traditional delivery for persistent, in situ production of these therapeutics.

 

For Zoom meeting details, please contact Maggie Berg.

Cancer and Microbes Seminar Series | Mar. 21, 12 - 1 p.m.

Examining changes in the gastrointestinal microbiome at pre-neoplastic stages of the adenoma
Presenter:  Christopher Gaulke, assistant professor of pathobiology

Brief description: Colorectal cancer (CRC) is a leading cause of cancer-related mortality and is associated with advanced age as well as environmental, hereditary, dietary and behavioral factors. Emerging evidence indicates that gut microbiome disruption also associates with CRC. Since CRC follows the adenoma-carcinoma sequence identifying microbial changes that occur at this stage may identify diagnostic markers of CRC risk or targets for preventative therapies. In this presentation Dr Gaulke will discuss his collaborations examining changes in the gastrointestinal microbiome at pre-neoplastic stages of the adenoma in a cohort of patients undergoing screening colonoscopy. These studies indicate that while fecal and oral microbial communities were poor diagnostics of adenoma formation, a random forest classifier built from mucosal microbial community abundances  reliably diagnosed adenoma formation (AUC = 0.993; out-of-bag error = 3.2%). The accuracy of this classifier was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. Dr Gaulke will further discuss his ongoing collaborations that seek to understand the mechanistic underpinnings of these associations and to determine if microbiome targeted interventions can reduce risk of CRC.

 

For Zoom meeting details, please contact Maggie Berg.

Cancer and Microbes Seminar Series | Feb. 7, 2022, 12 - 1 p.m.

Expansion microscopy to visualize neuronal F-actin ring 
Presenter:  Md Saddam Hossain Joy

Brief description: Expansion Microscopy (ExM) is a recent super-resolution microscopic technique that enables the visualization of sub-diffraction limited structures using a conventional optical microscope by physically enlarging the biological specimen itself. We are using this technique to visualize the recently discovered neuronal F-actin ring structure along the axon of the Drosophila larval motor neurons. These rings are approximately 200 nm apart from each other. However, many questions about these F-actin rings are still to be answered, like why 200 nm? and how the neurons maintain this 200 nm? We are using Expansion microscopy (ExM) to answer these questions. Once we establish the ExM technique, it can be used for cancer research, like better understanding the 3D neuronal cancer microenvironment.

 

Investigate if liver cancer-associated microbiota modulate bile acid signaling in the gut
Presenter:  Francois Reichardt

Brief description: Hepatocellular Carcinoma is associated with gut dysbiosis, favoring secondary bile acids production in the distal ileum. These bile acids are less potent activators of intestinal Farnesoid X Receptor, a known endogenous receptor of bile acids. Ileum organoids allow us to study the impact of different types of bile acids or microbiota by recreating in vitro enterocyte – bile acids – bacteria interactions and enable us to examine FXR signaling in ileal enterocytes.”

 

For Zoom meeting details, please contact Maggie Berg.