Johanning, Gary L.

Johanning, Gary L. Ph.D.

Selected Publications  |  Search PubMed  |  Contact

Research Interests

Vitamins and chemotherapy, cisplatin resistance genes, vitamins and cancer prevention, hyperinsulinemia, obesity and cancer, acyl coenzyme A binding protein, folic acid and cell-mediated immunity

Current Research

The major goal of the research in our laboratory is to determine the role of the vitamin folic acid (folate) in carcinogenesis and cancer prevention. An important aspect of this research is evaluating the influence of folic acid on the development of resistance to cisplatin and other chemotherapeutic agents. Cancer cells can become resistant to the cytotoxic action of chemotherapeutic agents either at the outset (intrinsic resistance) or after the agents are administered for a period of time (acquired resistance). Resistance to cisplatin and other agents is an important problem in cancer therapy, and the mechanism by which resistance develops is not clear. We have data indicating that folic acid can prevent the development of both intrinsic and acquired resistance to cisplatin in lung and ovarian cancer cell lines.

Our cDNA microarray analysis identified several candidate genes that are associated with the development of resistance to cisplatin. These include interferon-inducible protein 9-27, stromelysin 3, erbB-3 receptor protein-tyrosine kinase, and macrophage inhibitory cytokine 1. These genes have not previously been associated with the development of resistance to cisplatin. Our current focus is to determine whether manipulation of expression of these genes will modulate cisplatin resistance. We also performed cDNA microarray analysis of folate-depleted cells treated with cisplatin, to screen for novel differentially expressed genes. We found that expression of metallothionein-III, ciliary neuronotrophic factor and notch 4 is altered in cisplatin-treated cells, after depletion of folate from the cell culture media. Changes in expression of these genes may help explain the enhanced survival of cells and intrinsic resistance to cisplatin observed when cells are grown in medium depleted of folate. We are currently determining whether folic acid normalizes expression of these candidate genes as part of the mechanism whereby folic acid blocks development of resistance to cisplatin. We are also studying cisplatin treatment and folic acid depletion in relation to apoptosis, as well as folic acid and cisplatin transport in lung and ovarian cancer cells. The implication of this research is that a vitamin supplement may have efficacy in preventing development of resistance to cisplatin in lung and ovarian cancer cells.

Another ongoing research project in our laboratory is evaluation of acyl CoA binding protein (ACBP) expression in cancer. We are currently focusing on whether overexpression of ACBP causes changes in normal cells that lead to cell transformation and tumorigenesis. This work is particularly intriguing because a strong connection has recently been established between obesity and several types of cancer. Since ACBP is involved in binding fatty acids, and has been implicated in several types of cancer, it may provide a link between obesity and cancer. It may be that activation of genes involved in fat metabolism or obesity, such as ACBP, will also lead to changes in expression of oncogenes or tumor suppressor genes.

Our laboratory is working toward establishing an animal model of hyperinsulinemia, obesity and cancer. When rats are artificially reared by feeding a high-carbohydrate diet by stomach tube during the preweaning period, and thereafter fed lab chow, the rats become hyperinsulinemic, gradually gain weight, have abnormal glucose tolerance and eventually become obese, relative to normally-reared rats and rats artificially reared on a high-fat diet. Similarly, when rodents are fed a high-fat or high-carbohydrate diet prior to and during pregnancy, their progeny develop hyperinsulinemia and become obese in later life. We are testing the hypothesis that rodents who develop hyperinsulinemia and obesity in later life, as a result of early exposure to a hyperinsulinemic environment, will have increased N-methyl-N-nitrosourea-induced mammary tumor incidence and altered gene expression, compared to rats artificially reared on a non-hyperinsulinemic diet. We further hypothesize that hyperinsulinemia-induced increases in tumorigenesis are mediated by changes in mitochondrial function.

Selected Publications

  1. Piyathilake CJ, Azrad M, Macaluso M, Johanning GL, Cornwell PE, Partridge EE, Heimburger DC. Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status, Nutrition, 23 (3), 229-35, 2007
  2. Wang-Johanning F, Huang M, Liu J, Rycaj K, Plummer JB, Barnhart KF, Satterfield WC, Johanning GL. Sheep stromal-epithelial cell interactions and ovarian tumor progression, Int J Cancer, 121 (10), 2346-54, 2007
  3. Wang-Johanning F, Liu J, Rycaj K, Huang M, Tsai K, Rosen DG, Chen DT, Lu DW, Barnhart KF, Johanning GL. Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer, Int J Cancer, 120 (1), 81-90, 2007
  4. Whiteside MA, Piyathilake CJ, Bushell TM, Johanning GL. Intrinsic cisplatin resistance in lung and ovarian cancer cells propagating in medium acutely depleted of folate, Nutr Cancer, 54 (2), 274-84, 2006
  5. Henao OL, Piyathilake CJ, Waterbor JW, Funkhouser E, Johanning GL, Heimburger DC, Partridge EE. Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3, Int J Cancer, 113 (6), 991-7, 2005
  6. Whiteside MA, Chen DT, Desmond RA, Abdulkadir SA, Johanning GL. A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance, Oncogene, 23 (3), 744-52, 2004
  7. Wang-Johanning F, Frost AR, Jian B, Azerou R, Lu DW, Chen DT, Johanning GL. Detecting the expression of human endogenous retrovirus E envelope transcripts in human prostate adenocarcinoma, Cancer, 98 (1), 187-97, 2003
  8. Wang-Johanning F, Frost AR, Jian B, Epp L, Lu DW, Johanning GL. Quantitation of HERV-K env gene expression and splicing in human breast cancer, Oncogene, 22 (10), 1528-35, 2003
  9. Rodriguez-Burford C, Steele VE, Anderson AS, Stockard CR, Weiss HL, Eto I, Johanning GL, Grizzle WE, Grubbs CJ. Effects of body weight gain reduction resulting from chemopreventive agent treatment on mammary gland morphology, Nutr Cancer, 43 (1), 67-75, 2002

Contact Information


Mailing Address: Route 2, Box 151-B1, Bastrop, Texas 78602
Phone: (512) 321-3991