Dr. Jacalyn M. Green

Professor of Biochemistry


Midwestern University
Chicago College of Osteopathic Medicine
College of Dental Medicine- Illinois
Department of Biochemistry
Science Hall 421-K
555 31st St.
Downers Grove, IL 60515


Office: (630) 515-6155
e-mail: jgreen@midwestern.edu

EDUCATION

B.S. Chemistry University of Dayton (Dayton, OH) 1982
Ph.D. Biological Chemistry The University of Michigan (Ann Arbor, MI)      1988

RESEARCH SUMMARY

Folic Acid Metabolism Folic acid is a water soluble vitamin that is biologically active in its reduced forms, which act as one-carbon carriers in the biosynthesis of DNA, RNA, and amino acids. Folic acid is synthesized in plants and bacteria, and is required by humans. The importance of this vitamin in support of cell division in both prokaryotes and eukaryotes has resulted in many clinical applications.  These include the development of antibiotics which target folate biosynthesis in bacteria, and chemotherapeutic drugs which target folate utilization in rapidly dividing cells.  Folate also acts as a one-carbon carrier essential to DNA methylation, and therefore impacts epigenetic regulation of gene expression;  this is increasingly recognized to play an important role in carcinogenesis. 

Folic acid metabolism in cancer, using an established mouse model of oral cancer. This project is in collaboration with Dr. Joanna Goral (CCOM, Anatomy), Dr. Mae Ciancio (CHS) and Dr. Bruno Jham (CDMI). Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of death by cancer world-wide. Unfortunately, diagnosis is often made at advanced stages, resulting in a poor prognosis for patients.  Risk factors include use of tobacco products, alcohol consumption, and infection by human papillomavirus.   We hypothesize that nutritional factors may also contribute to disease progression:  we are interested in the effects of a diet high in fat or low in fat, and in the effects of folate deficiency versus folate adequacy. We have completed work with an established mouse model of oral cancer in which a carcinogen mimicked the effects of smoking to investigate whether a high fat diet or poor folic acid nutrition contribute to disease onset and progression.  While work with the animals has been completed, analysis of the tissues continues, and involves using imunohistochemistry to measure protein expression in tissue sections.  We are interested in determining whether this established model of oral cancer may also extend to cancer in other organs as well.  Proteins of interest include inflammatory markers (primarily in tissues from animals fed a high fat or low fat diet) and folate transport proteins (primarily in tissues from animals fed a folate-deficient or folate-sufficient diet). Completion of this study may lead to better diagnostic tools or dietary interventions for prevention.

Folate catabolism in bacteria. An additional focus of our laboratory is the investigation of  bacterial folate catabolism, using Escherichia coli as a model system.  Bacterial biosynthesis of folate is well understood, and has yielded many clinical applications in the form of antibiotics.  In contrast, folate catabolism has been much less studied. We study the abg operon of E. coli which encodes proteins involved in uptake and cleavage of folate catabolite p-aminobenzoyl-glutamate (PABA-GLU).  Our laboratory has demonstrated that transport protein AbgT imports PABA-GLU, and PABA-GLU hydrolase (PGH), an AbgA2AbgB2 hetero-tetramer, cleaves it into PABA and glutamate.  Divergently transcribed from the abg operon is the gene encoding the transcriptional regulator AbgR.  This operon is present only in E. coli and its close relatives, and there are intriguing patterns of differences in the sequences among these strains that suggest that the genes/proteins of the abg operon may play a role in determining the virulence of the most pathogenic members.  E. coli strains range in pathogenicity, ranging from the benign E. coli K12 strains to those causing urinary tract infections to those causing hemolytic uremic syndrome.  In addition, antibiotic resistance is a growing problem in medicine; any pathway that is important to the pathogen and absent in the human host offers a potential anti-bacterial target. 

Current Research Projects

Characterization of the expression of inflammatory markers in tissue sections from male and female mice fed a high fat or low fat diet, and exposed to a carcinogen (4NQO) or vehicle in their drinking water.   Past students have generated sets of slides containing samples from  liver, kidney, pancreas and spleen;  these sets of slides need to be analyzed for inflammatory markers for macrophages, neutrophils, and T cells.  These projects involve completing the immunohistochemical staining, observing the slides and noting qualitative features, photographing the slides, and scoring the slides for expression. Depending on the time commitment, one student can analyze one organ for one to three proteins. 

Characterization of the expression of folate transport proteins in tissue sections from male and female mice fed a folate-deficient or folate-adequate  diet, and exposed to a carcinogen (4NQO) or vehicle in their drinking water.   Past students have generated sets of slides containing samples from  liver, kidney, pancreas and spleen;  these sets of slides need to be analyzed for expression of the reduced folate carrier, folate receptors, and the proton-coupled folate transporter.  These projects involve completing the immunohistochemical staining, observing the slides and noting qualitative features, photographing the slides, and scoring the slides for expression. Depending on the time commitment, one student can analyze one organ for one to three proteins. 

Selected publications  (for an expanded list of publications, click here)

  1. Comparison of Substrate Specificity of Escherichia coli p-Aminobenzoyl-glutamate Hydrolase with Pseudomonas Carboxypeptidase G. (2014)  Larimer, C.M., Slavnic, D., Pitstick, L.D., and Green, J.M. Advances in Enzyme Research, 2, 39-48. http://dx.doi.org/10.4236/aer.2014.21004 click here for full text
  2. Glucarpidase to combat toxic levels of methotrexate in patients.(2012) Green, J.M. Ther. Clin. Risk Manag. 8:403-13. doi: 10.2147/TCRM.S30135. Epub 2012 Nov 22. PMID: 23209370  click here for full text link
  3. Purification and characterization of the folate catabolic enzyme p-aminobenzoyl-glutamate hydrolase from Escherichia coli.(2010) Green. J.M., Hollandsworth. R., Pitstick. L., Carter. E.L.J. Bacteriol. 192(9):2407-13. doi: 10.1128/JB.01362-09. Epub 2010 Feb 26. PMID:20190044  click here for full text link
  4. Escherichia coli abg genes enable uptake and cleavage of the folate catabolite p-aminobenzoyl-glutamate. (2007) Carter, E.L., Jager. L., Gardner. L., Hall. C.C., Willis. S., Green. J.M. J Bacteriol. 189(9):3329-34. Epub 2007 Feb 16. PMID:17307853  click here for full text link
  5. Characterization of mutations that allow p-aminobenzoyl-glutamate utilization by Escherichia coli. (1998) Hussein, M.J., Green, J.M., Nichols, B.P.  J Bacteriol. 180(23):6260-8. PMID: 9829935, click here for full text li