Arti Shukla, Ph.D.

Research Assistant Professor of Pathology

Research Program: Cell Signaling
VCC Membership Level: Full Member

Contact Information

216 HSRF
149 Beaumont Avenue
niversity of Vermont
Burlington, VT, 05405

ph: (802) 656-8253
f: (802) 656-8892
Arti.Shukla@uvm.edu

Biography

Dr. Shukla received her Ph.D. in Biochemistry from Banares Hindu University in 1988. She was a post-doctoral research associate at the University of Michigan, and a scientist (Pool Officer) and scientist-fellow at the Central Drug Research Institute in Luchnow, India, before coming to UVM in 1997 as a visiting scientist. She is currently a research assistant professor in the Department of Pathology.

Research

Malignant mesotheliomas (MMs) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal. It is an aggressive tumor derived from mesothelial cells. The mechanisms involved in the initiation and development of MMs are under intense investigation. Although traditionally recognized as associated with occupational asbestos exposure, MMs can appear in individuals with no documented exposure to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus (SV40) infections also facilitate development of MMs. The interest in this peculiar, phenotypically diverse cancer arises from the fact that its incidence is increasing worldwide, it causes profound morbidity and nearly universal mortality that is often refractory to conventional treatment modalities of aggressive surgery, radiotherapy, or chemotherapy. MM is presently a worldwide problem. In the UK mortality from MM is likely to more than double over the next 20 years and despite advances in surgery, chemotherapy and radiation treatment the overall prognosis for patients remain poor. Thus, MM represents a great challenge to clinicians and cancer researchers due to its poor prognosis and marked resistance to current therapies.

It is believed that MM is a malignancy caused by the interaction of environmental carcinogens (asbestos and erionite), viruses (SV40) and genetic predisposition. Dr. Shukla is trying to elucidate possible mechanisms of asbestos and SV40 carcinogenesis and co-carcinogenesis. Mechanistically, Dr. Shukla is focusing her investigations on how ERK cell signaling pathway plays a role in the development of MM. Her previous work showed that crocidolite asbestos and erionite carcinogenesis are linked to the ability of these minerals to induce the MAPK and ERK pathways which lead to AP-1 activation. Dr. Shukla's focus is on CREB, ERK1/2 and ERK5 and Jun/Fos family members as these proteins are critical targets of asbestos–induced carcinogenesis.

Recent Publications

Arti Shukla, Karen M. Lounsbury, Trisha F. Barrett, Joanna J. Gell, Mercedes Rincon, Kelly J. Butnor, Douglas J. Taatjes, Gerald S. Davis, Pamela Vacek, Keiichi I. Nakayama, Keiko Nakayama, Chad Steele and Brooke T. Mossman. Asbestos-induced peribronchiolar cell proliferation, cytokine production, and fibrosis are attenuated in lungs of protein kinase C-delta (PKC delta) knockout mice. American J Pathol, 170, 140-151, 2007.

Astrid Haegens, Trisha F. Barrett, Joanna Gell, Arti Shukla, Maximilian MacPherson, Pamela Vacek, Mathew E. Poynter, Kelly J. Butnor, Yvonne M. Janssen-Heininger, Chad Steele and Brooke T. Mossman. Airway epithelial NFkB activation modulates asbestos-induced inflammation and mucin production in vivo. J Immunology, 178 (3): 1800-1808 2007.

Christy A. Barlow, Trisha F. Barrett, Arti Shukla, Brooke T. Mossman and Karen M. Lounsbury. Asbestos-mediated CREB phosphorylation is regulated by protein kinase A and Extracellular regulated kinases 1/2. Am. J. Physiol. LCMP, 292: L1361-L1369, 2007.

Brooke T. Mossman, Arti Shukla and Naomi Fukagawa. Commentary on "Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles", by Beck-Speier, N. Dayal, E. Karg, K.L. Maier, G. Schumann, H. Schulz, M. Semmler, S. Takenaka, K. Stettmaier, W. Bors, A. Ghio, J.M. Samet, J. Heyder. Free Rad Biol Med, 43: 504-505, 2007.

Christy Barlow, Arti Shukla, Brook T Mossman and Karen M. Lounsbury. Oxidant-mediated cAMP response element binding protein activation. Calcium regulation and role in apoptosis of lung epithelial cells. Am J Resp. Cell Mol Biol, 34, 7-14, 2006.

Arti Shukla, Trisha F. Barrett, Keiichi I. Nakayama, Keiko Nakayama, Brooke T. Mossman and Karen M. Lounsbury. Transcriptional upregulation of MMPs 12 and 13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung. FASEB J, 20, 1-10, 2006.

Arti Shukla, Pamela Vacek and Brooke T. Mossman. Dose response relationships in expression of biomarkers of cell proliferation in In vitro assays and inhalation experiments. Nonlinearity Biol. Tox. Med, 2, 117-128, 2004.

Arti Shukla, Trisha Flanders, Karen M. Lounsbury and Brooke T. Mossman. Gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Cancer Research, 64, 7780-7786, 2004.

Arti Shukla and B.T. Mossman. Asbestosis and lung cancer: Role of reactive species, In; Reactive Oxygen /Nitrogen Species: Lung Injury and Disease, Eds.V.Vallyathan, V. Castranova and X. Shi. 187, 179-195, Marcel Dekker Inc, New York. Basel 2004.

M. Li, B. T. Mossman, E. Kolpa, C. R. Timblin, Arti Shukla, D. J. Taatjes and N. K. Fukagawa. Age-related differences in MAP kinase activity in VSMC in response to glucose or TNF-alpha. J Cell Physiol. 197, 418-425 (2003).

Arti Shukla, M. Stern, K. M. Lounsbury, T. Flanders and B.T. Mossman. Asbestos-induced apoptosis is protein kinase C delta dependent. Am J Resp Cell Mol Biol, 29,198-205 (2003)

Arti Shukla, M. Jung, M. Stern, N.K. Fukagawa, D.J. Taatjes, D. Sawyer, B. Van Houten and B.T. Mossman. Asbestos induces mitochondrial DNA damage and dysfunction linked to the development of apoptosis. Am J Physiol (Lung Cell Mol. Physiol) 285, L1018-25, (2003).

C. Timblin, Arti Shukla, I. Berlanger, K. A. BeruBe, A. Churg and B.T. Mossman. Ultrafine airborne particles cause increases in protooncogene expression and proliferation in alveolar epithelial cells. Toxicol. Appl. Pharmacol. 179, 98-104 (2002).

A.K. Hubbard, C. R. Timblin, Arti Shukla, M. Rincon, B.T. Mossman. Activation of NF-kB-dependent gene expression by silica in lungs of luciferase reporter mice. Am J Physiol Lung Cell Mol Physiol 282, L968-L975 (2002).

Other Key Publications

Arti Shukla, C.R. Timblin, A. Hubbard, J. Bravman and Brooke T. Mossman. Silica-induced activation of c-jun-NH2-terminal amino kinases, protracted expression of the activator protein-1 protooncogene, fra-1, and S-phase alterations are mediated via oxidative stress. Cancer Res 61 (5), 1791-1795 (2001).

G. S. Shukla, Arti Shukla, R.J. Potts, M. Ozier, B.A. Hart and J-F Chiu. Cadmium-mediated oxidative stress in alveolar epithelial cells induces the expression of γ-glutamylcysteine synthetase catalytic subunit and glutathione S-transferase α and π isoforms: Potential role of activator Protein-1. Cell Biol & Toxicol 16, 347-362 (2000).

Arti Shukla, C. Timblin, K. BeruBe, T. Gordon, W. McKinney, K. Driscoll, P. Vacek and B. T. Mossman. Airborne particulate matter causes expression of nuclear factor-kB-related genes after inhalation. Am J Respiratory Cell Mol Biol 23, 182-187 (2000).

B. T. Mossman, A. Hubbard, Arti Shukla and C. R. Timblin. Role of mitogen-activated protein kinases, early response protooncogenes, and activator protein-1 in cell signaling by asbestos. Inhal Toxicol 12 (suppl. 3), 307-316 (2000).

B. A. Hart, C. H. Lee, G. S. Shukla, Arti Shukla, M. Osier, J. D. Eneman and J. F. Chiu. Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress. Toxicology 133, 43-58 (1999).