Ian A. Blair, Ph.D.

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A.N. Richards Professor of Pharmacology
Department: Pharmacology
Graduate Group Affiliations

Contact information
854 Biomedical Research Building II/III
University of Pennsylvania School of Medicine
Center for Cancer Pharmacology
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: (215) 573-9880
Fax: (215) 573-9889

Cambridge Grammar School for Boys, United Kingdom , 1960.

Prince of Wales School, Nairobi, Kenya, 1963.
B.Sc. ((Special) Chemistry, ARCS)
Imperial College of Science and Technology, University of London, United Kingdom, 1968.
Imperial College of Science and Technology, University of London, United Kingdom, 1971.
MRSC (Organic Chemistry)
Adelaide University, Australia, 1972.
Australian National University, 1977.
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Description of Research Expertise

Establish the use of high-resolution mass spectrometry and molecular biology as tools for conducting sophisticated proteomics, DNA-adductomics, metabolomics, and lipidomics research with a particular emphasis on discovering biomarkers for the early detection of cancer and biomarkers of response in rare diseases

1. Early detection biomarkers of asbestos exposure, mesothelioma, and non-small lung cancer,

Amyloid β-peptides and high-mobility group box 1 (HMGB1) a non-histone chromosomal protein are the two most intensively studied endogenous cellular danger signals known as danger-associated molecular pattern (DAMP) molecules. DAMPs together with pathogen-associated molecular patterns alert the innate immune system by activating signal transduction pathways through binding to pattern recognition receptors (PRRs). PRRs include the receptor for advanced glycation end products (RAGE), toll-like receptors (TLRs), chemokine (C-X-C motif) receptor (CXCR), and T cell immunoglobulin mucin (TIM). Binding to PRRs induces pro-inflammatory cascades, which trigger the release of cytokines. PRRs are expressed by cells of the innate immune system such as macrophages, leukocytes and dendritic cells. They are also expressed on the surface of vascular cells, fibroblasts and epithelial cells. We have recently demonstrated that HMGB1 is secreted when blood is allowed to clot. Numerous studies have reported that HMGB1 is secreted in o the circulation by cancer patients. However, many of these studies are flawed because they used serum instead of plasma. Furthermore there are 29 reported sites of acetylation on HMGB1 so it is essential that the methodology is available to quantify each of the individual proteoforms. We are currently developing an approach for the analysis of HMGB1 proteoforms in plasma samples from patients with mesothelioma and non-small cell lung cancer as well as subjects who had a heavy exposure to asbestos. We are also quantifying lipid hydroperoxide-mediated DNA damage in lymphocytes from the same population in order to further understand the etiology of the disease. Finally, metabolomics and lipidomics studies are being conducted in order to discover additional biomarkers.

2. Biomarkers of therapeutic response in rare diseases.

There are > 40 rare genetic diseases that result from aberrant protein expression including, Duchene’s muscular dystrophy (DMD), spinocerebellar ataxia 1 (SCA-1), and Friedreich’s ataxia (FA). Current approaches to developing therapies for these rare diseases primarily involve increasing expression of the normal protein. The necessity for monitoring protein levels was highlighted recently during the US Food and Drug Administration (FDA) fast-track approval process for the drug eteplirsen (Exondys 51) to treat DMD. The lack of a rigorously validated method to assess up-regulation of dystrophin levels in DMD patients made it difficult to show a therapeutic response. FA is characterized by slowly progressive ataxia and hypertrophic cardiomyopathy. Lifespan is significantly reduced in FA with an average of death of 37-years, most commonly from cardiac-related pathologies. There are no approved treatments for FA, although numerous experimental approaches are being tested, which primarily involve up-regulation of frataxin protein. We have developed a strategy to monitor improvements in mitochondrial metabolism using FA platelets. We are now developing more direct measure of frataxin expression. This will also provide an approach to monitor new therapies that are being developed for rare genetic diseases of aberrant protein expression such as DMD24 and SCA-1.

Selected Publications

Napierala, J. S., Rajapakshe, K., Clark, A., Chen, Y. Y., Huang, S., Mesaros, C., Xu, P., Blair, I. A., Hauser, L. A., Farmer, J., Lynch, D. R., Edwards, D. P., Coarfa, C., Napierala, M.: Reverse Phase Protein Array Reveals Correlation of Retinoic Acid Metabolism With Cardiomyopathy in Friedreich''s Ataxia. Mol Cell Proteomics 20: 100094, May 2021.

Yu, W., Gillespie, K. P., Chhay, B., Svensson, A. S., Nygren, P. A., Blair, I. A., Yu, F., Tsourkas, A.: Efficient Labeling of Native Human IgG by Proximity-Based Sortase-Mediated Isopeptide Ligation. Bioconjug Chem 32(6): 1058-1066, May 2021.

Asangani, I., Blair, I. A., Van Duyne, G., Hilser, V. J., Moiseenkova-Bell, V., Plymate, S., Sprenger, C., Wand, A. J., Penning, T. M.: Using biochemistry and biophysics to extinguish androgen receptor signaling in prostate cancer. J Biol Chem 296: 100240, January 2021.

Zhang, Y., Xu, Y., Lu, W., Ghergurovich, J. M., Guo, L., Blair, I. A., Rabinowitz, J. D., Yang, X.: Upregulation of Antioxidant Capacity and Nucleotide Precursor Availability Suffices for Oncogenic Transformation. Cell Metab 33(1): 94-109 e8, January 2021.

McAndrew, N. P., Bottalico, L., Mesaros, C., Blair, I. A., Tsao, P. Y., Rosado, J. M., Ganguly, T., Song, S. J., Gimotty, P. A., Mao, J. J., DeMichele, A.: Effects of systemic inflammation on relapse in early breast cancer. NPJ Breast Cancer 7(1): 7, January 2021.

Quinn, W. J., 3rd, Jiao, J., TeSlaa, T., Stadanlick, J., Wang, Z., Wang, L., Akimova, T., Angelin, A., Schafer, P. M., Cully, M. D., Perry, C., Kopinski, P. K., Guo, L., Blair, I. A., Ghanem, L. R., Leibowitz, M. S., Hancock, W. W., Moon, E. K., Levine, M. H., Eruslanov, E. B., Wallace, D. C., Baur, J. A., Beier, U. H.: Lactate Limits T Cell Proliferation via the NAD(H) Redox State. Cell Rep 33(11): 108500, December 2020.

Chandramouleeswaran, P. M., Guha, M., Shimonosono, M., Whelan, K. A., Maekawa, H., Sachdeva, U. M., Ruthel, G., Mukherjee, S., Engel, N., Gonzalez, M. V., Garifallou, J., Ohashi, S., Klein-Szanto, A. J., Mesaros, C. A., Blair, I. A., Pellegrino da Silva, R., Hakonarson, H., Noguchi, E., Baur, J. A., Nakagawa, H.: Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes. PLoS One 15(9): e0239625, September 2020.

Weng, L., Laboureur, L., Wang, Q., Guo, L., Xu, P., Gottlieb, L., Lynch, D. R., Mesaros, C., Blair, I. A.: Extra-mitochondrial mouse frataxin and its implications for mouse models of Friedreich''s ataxia. Sci Rep 10(1): 15788, September 2020.

Alicea, G. M., Rebecca, V. W., Goldman, A. R., Fane, M. E., Douglass, S. M., Behera, R., Webster, M. R., Kugel, C. H., 3rd, Ecker, B. L., Caino, M. C., Kossenkov, A. V., Tang, H. Y., Frederick, D. T., Flaherty, K. T., Xu, X., Liu, Q., Gabrilovich, D. I., Herlyn, M., Blair, I. A., Schug, Z. T., Speicher, D. W., Weeraratna, A. T.: Changes in Aged Fibroblast Lipid Metabolism Induce Age-Dependent Melanoma Cell Resistance to Targeted Therapy via the Fatty Acid Transporter FATP2. Cancer Discov 10(9): 1282-1295, June 2020.

Li, F., Huangyang, P., Burrows, M., Guo, K., Riscal, R., Godfrey, J., Lee, K. E., Lin, N., Lee, P., Blair, I. A., Keith, B., Li, B., Simon, M. C.: FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome. Nat Cell Biol 22(6): 728-739, June 2020.

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Last updated: 06/23/2021
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