John R. Porter PhD

John R. Porter

John R. Porter PhD

Director, Graduate Program in Biological Sciences

Professor of Biology
Research Professor of Pharmacognosy

Education

BS (Pittsburg State)

PhD (University of Montana)

Postdoctoral Research Fellow (University of Nebraska-Lincoln)

Research Interests

Molecular analysis of the production of the anti-cancer compound podophyllotoxin by plant endophytic fungi

Analysis of the proteasome of Mycobacterium tuberculosis as a therapeutic target

Studies of compounds that induce biliary atresia

Discovery of antimicrobial, antifungal and anticancer natural products

Synopsis

We work at the interface among cell biology, biotechnology and natural products biology/chemistry. We are actively pursuing alternate sources for known medicinal compounds, discovery of novel medicinal compounds, and application of natural products to specific targets for antimicrobial therapy.

Alternate sources of natural products

We work with various fungi and transformed plant roots that can produce impressive arrays and quantities of medicinal natural products. We are investigating the production of podophyllotoxin, precursor to several anticancer drugs, by endophytic fungi  found growing in tissues of the source plant, Podophyllum peltatum. Our current research is aimed to fully understand the biosynthesis in these fungi by molecular analysis of the genes responsible and transfer these genes to organisms that grow more rapidly and predictably. We have used Agrobacterium rhizogenes plant transformation to grow “hairy roots” for production of medicinal natural products. Our goal is to understand the range of compounds produced, identify novel compounds, and determine their biological activities. Completed projects include production of valepotriates, solasodine, isolation and characterization of endophytic fungi that produce podophyllotoxin, and characterization of chromosomal virulence genes in A. rhizogenes, . We also work to isolate, identify, and determine biological activities of natural products from various sources. We use materials we collect as well as extracts from the National Cancer Institute Open Repository of natural products extracts.

Biliary atresia

A human disease that affects the function of the bile duct in infants, biliary atresia is of unknown etiology.  We are working to understand the toxic compounds from a plant that causes a very similar syndrome in livestock.  Working with our collaborators at the Perelman School of Medicine, we are studying the effect of the extracts and purified compounds on zebrafish and mouse model systems.  Access to the compounds will provide an inducible animal model to allow testing of hypotheses related to the onset and causes of the human syndrome.

Targeted antimicrobial therapies

We have begun investigation of the mycobacterial proteasome as a target for therapies to combat tuberculosis, leprosy, and related diseases. Proteasomes are only found in some bacteria, and they are unique from mammalian proteasomes, making them ideal candidates for therapy. We are in the process of isolating functional proteasomes, development of high-throughput screening assays, and then assay of a variety of extracts and compounds of natural products origin. We plan to identify novel compounds that specifically inhibit mycobacterial proteasome activity, which will allow the patient the clear the infection by normal lysosomal processes.  Completed studies include analyses of the proteasomal gene operon under nitrosative stress and confirmation of gene sequences in the avirulent M. tuberculosis H37Ra model.

Selected Scholarly Activity

Gunderwala A, Porter J. A luminescence assay for natural product inhibitors of the Mycobacterium tuberculosis proteasome. Phytochem Anal. 2016 Jan 18. doi: 10.1002/pca.2607. PubMed PMID: 26778282.

Koo KA, Waisbourd-Zinman O, Wells RG, Pack M, Porter JR. Reactivity of biliatresone, a natural biliary toxin, with glutathione, histamine, and amino acids. Chem Res Toxicol. 2016 Jan 13. doi: 10. 1021/acs.chemrestox.5b00308. PubMed PMID: 26713899.

Gupta S, Marko MG, Miller VA, Schaefer FT, Anthony JR, Porter JR. Novel production of terpenoids in Escherichia coli and activities against breast cancer cell lines. Appl Biochem Biotechnol. 2015 Mar;175(5):2319-31. doi: 10.1007/s12010-014-1382-4. Epub 2014 Dec 9. PubMed PMID: 25484192.

Lorent K, Gong W, Koo KA, Waisbourd-Zinman O, Karjoo S, Zhao X, Sealy I, Kettleborough RN, Stemple DL, Windsor PA, Whittaker SJ, Porter JR, Wells RG, Pack M. Identification of a plant isoflavonoid that causes biliary atresia. Sci Transl Med. 2015 May 6;7(286):286ra67. doi: 10.1126/scitranslmed.aaa1652. PubMed PMID: 25947162.

Tian D, Porter JR. An Isoflavone from Leiophyllum buxifolium and Its Antiproliferative Effect. J Nat Prod. 2015 Jul 24;78(7):1748-51. doi: 10.1021/acs.jnatprod.5b00100. Epub 2015 Jun 18. PubMed PMID: 26086179.

Koo KA, Lorent K, Gong W, Windsor P, Whittaker SJ, Pack M, Wells RG, Porter JR. Biliatresone, a Reactive Natural Toxin from Dysphania glomulifera and D. littoralis: Discovery of the Toxic Moiety 1,2-Diaryl-2-Propenone. Chem Res Toxicol. 2015 Aug 17;28(8):1519-21. doi: 10.1021/acs.chemrestox.5b00227. Epub 2015 Jul 20. PubMed PMID: 26175131.

Arneaud SL, Porter JR. Investigation and Expression of the Secoisolariciresinol Dehydrogenase Gene Involved in Podophyllotoxin Biosynthesis. Mol Biotechnol. doi: 10.1007/s12033-015-9888-8. Epub 2015 Aug 20. PubMed PMID: 26289300.

Piechoski, M.P., Cundell, D.R., Bower, A.H., Porter, J.R.  “Bioassay and antibiotic activity of Jamaican soil isolates: Identification of narrow spectrum antibiotic compounds.”  Journal of Young Investigators (October): 26-32 (2012).

Porter, J.R.  “The continuing promise of natural products for drug development (invited guest editorial). American Biology Teacher 74(4): 210-211 (2012).

Porter, J.R. “ Podophyllum endophytic fungi.” in Medicinal Plant Biotechnology, R Arora, ed. CABI Publ., Wallingford, UK, Chap 12, pp 197-206 (2010).

Jaiswal, V., DerMarderosian, A., and Porter, J.R. “Anthocyanins and polyphenol oxidase from dried arils of pomegranate Punica granatum L.” Journal of Food Science 118: 11-16 (2010).

Porter, J.R. “Plant fungal endophytes: Interactions, metabolites and biosyntheses in R. Ikan, ed. Selected Topics in the Chemistry of Natural Products (ISBN 981-270-569-4). World Scientific Publ., Chap 15, pp 503-580 (2008).

Eyberger, A.L., Dondapati, R., and Porter, J.R. “Two endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin.” Journal of Natural Products 69(8), 1121-1124 (2006).

Porter, J.R. “Information literacy in biology education: An example from an advanced cell biology course.” Journal of Cell Biology Education 4, 335-343 (2005).

T.A. Al- Howiriny, A.J. Al-Rehaily, J.R. Pols, J.R. Porter, J.S. Mossa, B. Ahmed, "Three new diterpenes and biological activity of Jasonia montana," Nat. Prod. Res., 2005, 19(3):253-265.

Professional Information

Prior Positions

  • Visiting Assistant Professor, St. Lawrence University, Canton, NY, 1981-1982

  • Visiting Summer Faculty Research Fellow, NASA – Stennis Space Center, MS, 1990-1991

Memberships in Professional Organizations

  • American Association for the Advancement of Science

  • American Chemical Society

  • American Society for Microbiology

  • American Society of Pharmacognosy (Webmaster)

  • Phytochemical Society of North America

  • Sigma Xi

 

Contact Information

Office location: McNeil Science & Technology Center, Room 371
Mailing address: Box 38
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
Office Phone: 215.596.8917
Office Fax: 215.596.8710
Email:

j [dot] porter [at] usciences [dot] edu