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Krzysztof Reiss, PhD

Associate Professor, Neuroscience

Associate Professor, Neurovirology

Location: Room 753 MERB

Telephone:  215-707-6337

Fax:  215-707-4888

Email: kreiss@temple.edu

Department of Neuroscience

Center for Neurovirology

MS, Cell Biology - 1983

The Jagiellonian University

Cracow, Poland

 

PhD, Molecular Biology - 1988

The Jagiellonian University

Cracow, Poland

 

Habilitation, Molecular Biology - 1999

The Jagiellonian University

Cracow, Poland

 

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Signal transduction pathways with great emphasis on the function of insulin-like growth factor I receptor (IGF-IR) in cell proliferation, cell survival, DNA repair and malignant transformation.

Research Summary
The general focus of this laboratory is to investigate molecular pathways involved in the development of cancer with a specific interest in brain tumors. A major effort has been undertaken to utilize cell culture techniques, experimental animal models, and clinical samples to identify the role of cell cycle regulators, signal transduction molecules, growth factors, and viral proteins in the development of pediatric brain tumors including medulloblastomas, and glioblastomas. Results from these multiple studies led to the discovery of a strong association between human polyomavirus JC and CNS tumors; the detection of new pathologic changes in cellular pathways caused by viral proteins; and the development of novel protein-based strategies aiming against malignant growth and survival of tumor cell in the brain.

There are three major experimental projects are presently active in this laboratory: The first project focuses on the investigation of signaling pathways from insulin-like growth factor -1 receptor (IGF-IR) supporting survival of cancer cells in the condition of anchorage-independence - when cellular interactions with extracellular matrix proteins are restricted during metastatic spread. Since attenuation of the IGF-IR function in anchorage-independence compromises survival of cancer cells, we are investigating different strategies to attenuate its function. This includes: antisense strategies; RNA interference; and dominant negative mutants of the receptor, such as synthetic peptide that resembles C-terminal portion of the α?subunit; or soluble form of the α?subunit (486/STOP), engineered either to trigger apoptosis directly, or to compete with the IGF-I ligand binding to the endogenous receptor.

In the second project studies are aimed at the investigation of the functional interplay between IGF-IR signaling pathways and viral protein, large T-antigen, and its possible role in the development of genomic instability. Our results show that an early viral protein, JC T-antigen, inhibits faithful DNA repair with the involvement of homologous recombination (HRR), which causes accumulation of spontaneous mutations. Surprisingly, JC T-antigen does not interact with HRR directly. Instead, it translocates IRS-1 to the nucleus. In nuclear compartment IRS-1 binds Rad51 at the site of damaged DNA. Similarly, modified IRS-1 equipped with nuclear localization signal binds Rad51 in the absence of JC T-antigen. Our results suggest a novel mechanism, which may explain how this viral protein triggers genomic instability. It involves the inhibition of HRR by IRS-1, which in the presence of JC T-antigen interferes with the major HRR protein, Rad51, compromising its function at the site of DNA repair.

Finally in the third project we are investigating the neuroprotective function of the IGF-IR signaling system in the paradigm of HIV associated dementia (HAD). Results from our preliminary work strongly indicate that inflammatory cytokine TNFα plays a critical role in the process of neuronal damage associated with the presence of HIV infected macrophage/macroglia. Importantly, our in vitro neuronal models indicate that TNFα–induced damage is not accompanied by neuronal apoptosis, but rather with degeneration of neuronal processes. Since activated IGF-I receptor prevents degeneration of neuronal processes in this experimental setting, we are investigating whether and how signaling balance between IGF-I and TNFα affects the decision between neuronal death and neuronal survival.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19834489. Gualco E, Urbanska K, Perez-Liz G, Sweet T, Peruzzi F, Reiss K, Del Valle L, IGF-IR-dependent expression of Survivin is required for T-antigen-mediated protection from apoptosis and proliferation of neural progenitors. Cell Death Differ :()2009 Oct 16

19273072. Gualco E, Wang JY, Del Valle L, Urbanska K, Peruzzi F, Khalili K, Amini S, Reiss K, IGF-IR in neuroprotection and brain tumors. Front Biosci 14:(352-75)2009 Jan 1

19117011. Urbanska K, Pannizzo P, Lassak A, Gualco E, Surmacz E, Croul S, Del Valle L, Khalili K, Reiss K, Estrogen receptor beta-mediated nuclear interaction between IRS-1 and Rad51 inhibits homologous recombination directed DNA repair in medulloblastoma. J Cell Physiol 219:2(392-401)2009 May

18794852. Fiorilli P, Partridge D, Staniszewska I, Wang JY, Grabacka M, So K, Marcinkiewicz C, Reiss K, Khalili K, Croul SE, Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation. Lab Invest 88:11(1143-56)2008 Nov

18546270. Urbanska K, Pannizzo P, Grabacka M, Croul S, Del Valle L, Khalili K, Reiss K, Activation of PPARalpha inhibits IGF-I-mediated growth and survival responses in medulloblastoma cell lines. Int J Cancer 123:5(1015-24)2008 Sep 1

18281528. Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A, Medulloblastoma: from molecular pathology to therapy. Clin Cancer Res 14:4(971-6)2008 Feb 15

18247371. Darbinian N, Darbinyan A, Czernik M, Peruzzi F, Khalili K, Reiss K, Gordon J, Amini S, HIV-1 Tat inhibits NGF-induced Egr-1 transcriptional activity and consequent p35 expression in neural cells. J Cell Physiol 216:1(128-34)2008 Jul

17653096. Siddiqui K, Del Valle L, Morellet N, Cui J, Ghafouri M, Mukerjee R, Urbanska K, Fan S, Pattillo CB, Deshmane SL, Kiani MF, Ansari R, Khalili K, Roques BP, Reiss K, Bouaziz S, Amini S, Srinivasan A, Sawaya BE, Molecular mimicry in inducing DNA damage between HIV-1 Vpr and the anticancer agent, cisplatin. Oncogene 27:1(32-43)2008 Jan 3

17593555. Wang JY, Gualco E, Peruzzi F, Sawaya BE, Passiatore G, Marcinkiewicz C, Staniszewska I, Ferrante P, Amini S, Khalili K, Reiss K, Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes. J Neurosci Res 85:11(2360-73)2007 Aug 15

17431132. Rink L, Slupianek A, Stoklosa T, Nieborowska-Skorska M, Urbanska K, Seferynska I, Reiss K, Skorski T, Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cells. Blood 110:2(651-60)2007 Jul 15

17392168. Piña-Oviedo S, Urbanska K, Radhakrishnan S, Sweet T, Reiss K, Khalili K, Del Valle L, Effects of JC virus infection on anti-apoptotic protein survivin in progressive multifocal leukoencephalopathy. Am J Pathol 170:4(1291-304)2007 Apr

17385710. Caracciolo V, Reiss K, Crozier-Fitzgerald C, De Pascali F, Macaluso M, Khalili K, Giordano A, Interplay between the retinoblastoma related pRb2/p130 and E2F-4 and -5 in relation to JCV-TAg. J Cell Physiol 212:1(96-104)2007 Jul

17374989. Wang H, Wang M, Reiss K, Darbinian-Sarkissian N, Johnson EM, Iliakis G, Amini S, Khalili K, Rappaport J, Evidence for the involvement of Puralpha in response to DNA replication stress. Cancer Biol Ther 6:4(596-602)2007 Apr

17077388. Chintapalli J, Yang S, Opawumi D, Goyal SR, Shamsuddin N, Malhotra A, Reiss K, Meggs LG, Inhibition of wild-type p66ShcA in mesangial cells prevents glycooxidant-dependent FOXO3a regulation and promotes the survival phenotype. Am J Physiol Renal Physiol 292:2(F523-30)2007 Feb

17016438. Urbanska K, Trojanek J, Del Valle L, Eldeen MB, Hofmann F, Garcia-Echeverria C, Khalili K, Reiss K, Inhibition of IGF-I receptor in anchorage-independence attenuates GSK-3beta constitutive phosphorylation and compromises growth and survival of medulloblastoma cell lines. Oncogene 26:16(2308-17)2007 Apr 5

16936750. Caracciolo V, Reiss K, Khalili K, De Falco G, Giordano A, Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus. Oncogene 25:38(5294-301)2006 Aug 28

16741963. Darbinian-Sarkissian N, Czernik M, Peruzzi F, Gordon J, Rappaport J, Reiss K, Khalili K, Amini S, Dysregulation of NGF-signaling and Egr-1 expression by Tat in neuronal cell culture. J Cell Physiol 208:3(506-15)2006 Sep

16707598. Grabacka M, Plonka PM, Urbanska K, Reiss K, Peroxisome proliferator-activated receptor alpha activation decreases metastatic potential of melanoma cells in vitro via down-regulation of Akt. Clin Cancer Res 12:10(3028-36)2006 May 15

16572421. Trojanek J, Ho T, Croul S, Wang JY, Chintapalli J, Koptyra M, Giordano A, Khalili K, Reiss K, IRS-1-Rad51 nuclear interaction sensitizes JCV T-antigen positive medulloblastoma cells to genotoxic treatment. Int J Cancer 119:3(539-48)2006 Aug 1

16307448. Wang JY, Grabacka M, Marcinkiewicz C, Staniszewska I, Peruzzi F, Khalili K, Amini S, Reiss K, Involvement of alpha1beta1 integrin in insulin-like growth factor-1-mediated protection of PC12 neuronal processes from tumor necrosis factor-alpha-induced injury. J Neurosci Res 83:1(7-18)2006 Jan

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