My research involves the use of proteomic methodologies to investigate the biological basis of disease. We have two main focuses: characterizing the nature of pediatric Autism Spectrum Disorder (ASD), and understanding the nature of diseases of the urinary tract, including prostate cancer.

Although at one time considered an emotional disturbance resulting from early attachment experiences, ASD is now recognized as a disorder of prenatal and postnatal brain development. ASD is primarily a genetic disorder involving multiple genes, but insights into underlying mechanisms, and thus development of treatment options, requires a multidisciplinary approach. In our lab, proteomics is used to define molecular and protein signaling pathways that mediate both normal and abnormal development of language, social interaction, and cognitive and motor routines. Once these pathways are understood, repair mechanisms or treatment techniques can be developed to attempt to alleviate the symptoms before permanent damage occurs.

We are studying the biological basis of urinary tract disease using similar techniques as those of the ASD research. First, we are investigating the presence of Anti-Proliferative Factor (APF), a small peptide suspected to be involved in interstitial cystitis (IC), in urine samples of IC patients. Interstitial cystitis is a chronic bladder disorder of unknown etiology that results in severe, chronic pain in approximately 1:500 people in the US alone. Although the pathogenesis is still not understood, it has recently been shown that anti-proliferative factor affects bladder cell epithelium, specifically in interstitial cystitis patients.

The second urinary tract disease under analysis in our labs is prostate cancer, a significant male health problem in the Western world that is diagnosed in 300,000 men, and causes 30,000 deaths, annually. Proteomic technology is being used to identity such markers, which can lead to faster diagnosis, and thus a higher survival expectancy, for patients.

In the post-genomic era, genes and proteins are now studied on a more comprehensive scale. Studying disease processes at only the genetic or transcriptomic level will give an incomplete portrayal of disease manifestation because a single gene can be translated into potentially a thousand proteins, in addition to the complexities of post-translational medications for each protein. A proteomic approach allows for a more global overview of the effect of disease processes on the proteins present in cells, tissues and organisms, and thus a more directly relevant portrayal of the ability to cure disease.

Ryan EP, Bushnell TP, Friedman AE, Rahman I, Phipps RP. 2008. Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Cancer Immunol Immunother. Mar;57(3):347-358.

Michael G. Malkowski, Erin Quartley, Alan E. Friedman, Julie Babulski, Yoshiko Kon1, Jennifer Wolfley, Meriem Said, Joseph R. Luft, Eric M. Phizicky, George T. DeTitta, and Elizabeth J. Grayhack. 2007. Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing. Proc Natl Acad Sci U S A. Apr 17;104(16):6678-6683.

Robert D Bell, Abhay P Sagare, Alan E Friedman, Gurrinder S Bedi, David M Holtzman, Rashid Deane and Berislav V Zlokovic. 2007. Transport pathways for clearance of human Alzheimer’s amyloid beta peptide and apolipoproteins E and J in the mouse central nervous system. J Cereb Blood Flow Metab. May;27(5):909-918.

Detty, M R., Zhou, F., and Friedman, A. E. 1996. Positive Halogens from Halides and Hydrogen Peroxide with Organotellurium Catalysts. J. Am. Chem. Soc., 118, 313-318.

Wang, S., Friedman, A. E., and Kool, E.T. 1995. Origins of High Sequence Selectivity: A Stopped-flow UV Kinetics Study of Single-stranded Nucleic Acid Binding by Triplex-forming Oligonucleotides. Biochemistry, 34, 9774-9784.

Miller, V. P., Goodin, D. P., Friedman, A. E., and Ortiz de Montellano, P. R. 1995. Horseradish Peroxidase PHE-172 -> TYR Mutant: Sequential Formation of Compound I with a Porphyrin Radical Cation and a Protein Radical. J. Bio. Chem., 270, 18413-18419.

Detty, M.R., Friedman, A. E., and McMillan, M. 1995. Step-wise Mechanism for Oxidative Addition of Iodine to Organotellurium(II) Compounds. Organometallics, 14, 1422-1449.

Detty, M. , Friedman, A. E., and Oseroff, A. 1994. A Mechanism for the Oxidation of Glutathione to Glutathione Disulfide with Organotellurium(IV) and Organoselenium(IV) Compounds. A Step-wise Process with Implications for Photodynamic Therapy and Other Oxidative Chemotherapy. J. Org. Chem., 59, 8245-8250.

Friedman, A. E., Kumar, C. V., Turro, N. J., and Barton, J. K. 1991. Luminescence of ruthenium(II) polypyridyls: evidence for intercalative binding to Z-DNA. Nucleic Acids Res., 19, 2595-2602.

Friedman, A. E., Chambron, J. -C., Sauvage, J. -P., Turro, N. J., and Barton, J. K. 1990. Molecular ‘Light Switch’ for DNA: Ru(bpy)2(dppz)2+. J. Am. Chem. Soc. 112, 4960-4962.