Skip to Content

'
Victor Krasnykh, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX

Bio Statement

 Dr. Krasnykh’s research program includes three main directions: The development of viral vectors for tumor-specific delivery and expression of therapeutic and imaging transgenes, the development of a versatile virus-based platform for anti-cancer vaccination, and the development of targeted imaging probes for cancer detection.  

Viral vectors for tumor-specific gene delivery.   The focus of these efforts is on achieving efficient, safe, and truly tumor-specific gene delivery and expression. To this end, we modify the natural tropism (tissue specificity) of adenoviruses (Ad) by direct genetic engrafting of tumor-targeting ligands into Ad virion proteins or by designing recombinant bispecific protein adapters that cross-link the viral vector and the target biomarker on tumor cells to enable gene transfer.  In addition, we develop a more advanced strategy, which will eventually allow us to build extensive dual-function (protection and targeting) molecular shields on the surface of Ad virions resulting in protection of the virus from neutralization by antibodies, undesired uptake by nontarget tissues, and much improved targeting of tumors. 

Virus-based vaccines for anti-cancer immunization.   The goal here is to develop a versatile technological platform that will enable rapid generation of self-propagating vaccines that display sets of computationally predicted immunogenic epitopes of tumor-specific antigens (TSA) and are targeted to antigen-presenting cells (APCs) for improved processing . This will be achieved through multivalent presentation of defined TSA epitopes by genetically engrafting these epitopes in major proteins of viral particles. Targeting of these viral vaccines to APCs will be achieved by using the strategies described above

Tumor-targeted imaging probes . These efforts are centered on using the rationally designed protein scaffolds as a platform for companion imaging diagnostics of cancer. For instance , to make complete surgical removal of disseminated microscopic tumors possible , we are working on developing panels of tumor marker­ binding probes enabling both the pre-operative detection of tumors by positron­ emission tomography and the intraoperative localization and identification of tumors by near-infrared imaging .

 

Education & Training

Degree-Granting Education

1999 Division of Gene Therapy, Department of Medical Oncology, Free University of Amsterdam, Amsterdam, the Netherlands, PHD, Medical Science
1982 Novosibirsk State University, Novosibirsk, Russia, MS, Microbiology

Experience/Service

Academic Appointments

Associate Professor, The University of Texas, Graduate School of Biomedical Sciences, Houston, TX, 2009-present
Associate Professor, Department of Experimental Diagnostic Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 8/2003-6/2013

Selected Publications

Peer-Reviewed Original Research Articles

1. Belousova N, Mikheeva G, Xiong C, Stagg LJ, Gagea M, Fox PS, Bassett RL, Ladbury JE, Braun MB, Stehle T, Li C, Krasnykh V. Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43. Oncotarget. e-Pub 7/2016. PMID: 27462785.
2. Dreier B, Honegger A, Hess C, Nagy-Davidescu G, Mittl PR, Grütter MG, Belousova N, Mikheeva G, Krasnykh V, Plückthun A. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters. Proc Natl Acad Sci U S A 110(10):E869-77, 3/2013. e-Pub 2/2013. PMCID: PMC3593905.
3. Dreier B, Mikheeva G, Belousova N, Parizek P, Boczek E, Jelesarov I, Forrer P, Plückthun A, Krasnykh V. Her2-specific multivalent adapters confer designed tropism to adenovirus for gene targeting. J Mol Biol 405(405):410-426, 1/2011. e-Pub 11/2010. PMCID: PMC3149894.
4. Yeh HH, Ogawa K, Balatoni J, Mukhapadhyay U, Pal A, Gonzalez-Lepera C, Shavrin A, Soghomonyan S, Flores L, Young D, Volgin AY, Najjar AM, Krasnykh V, Tong W, Alauddin MM, Gelovani JG. Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT. Proc Natl Acad Sci U S A 108(4):1603-1608, 1/2011. e-Pub 1/2011. PMCID: PMC3029752.
5. Belousova N, Mikheeva G, Xiong C, Soghomonian S, Young D, Le Roux L, Naff K, Bidaut L, Wei W, Li C, Gelovani J, Krasnykh V. Development of a targeted gene vector platform based on simian adenovirus serotype 24. J Virol 84(19):10087-1001, 10/2010. e-Pub 7/2010. PMCID: PMC2937776.
6. Piao Y, Jiang H, Alemany R, Krasnykh V, Marini FC, Xu J, Alonso MM, Conrad CA, Aldape KD, Gomez-Manzano C, Fueyo J. Oncolytic adenovirus retargeted to Delta-EGFR induces selective antiglioma activity. Cancer Gene Ther 16(3):256-65, 3/2009. e-Pub 10/2008. PMCID: PMC3793894.
7. Glasgow JN, Mikheeva G, Krasnykh V, Curiel DT. A strategy for adenovirus vector targeting with a secreted single chain antibody. PLoS One 4(12):e8355, 2009. e-Pub 12/2009. PMCID: PMC2791226.
8. Wu Y, Fang B, Yang XQ, Wang L, Chen D, Krasnykh V, Carter BZ, Morris JS, Shureiqi I. Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer. Mol Ther 16(5):886-92, 5/2008. e-Pub 3/2008. PMCID: PMC2377397.
9. Belousova N, Mikheeva G, Gelovani J, Krasnykh V. Modification of adenovirus capsid with a designed protein ligand yields a gene vector targeted to a major molecular marker of cancer. J Virol 82(2):630-637, 1/2008. e-Pub 11/7/2007. PMCID: PMC2224583.
10. Hosokawa M, Kadota R, Shichijo S, Itoh K, Dmitriev I, Krasnykh V, Curiel DT, Takue Y, Wakasugi H, Takashima S, Heike Y. Cell cycle arrest and apoptosis induced by SART-1 gene transduction. Anticancer Res 25(3B):1983-1990, May-Jun, 5/2005. PMID: 16158934.
11. Wu H, Han T, Belousova N, Krasnykh V, Kashentseva E, Dmitriev I, Kataram M, Mahasreshti PJ, Curiel DT. Identification of sites in adenovirus hexon for foreign peptide incorporation. J Virol 79(6):3382-3390, 3/2005. PMCID: PMC1075677.
12. Wang M, Hemminki A, Siegal GP, Barnes MN, Dmitriev I, Krasnykh V, Liu B, Curiel DT, Alvarez RD. Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery. Gynecol Oncol 2(2):341-8, 2/2005. PMID: 15661219.
13. Ono HA, Davydova JG, Adachi Y, Takayama K, Barker SD, Reynolds PN, Krasnykh VN, Kunisaki C, Shimada H, Curiel DT, Yamamoto M. Promoter-controlled infectivity-enhanced conditionally replicative adenoviral vectors for the treatment of gastric cancer. J Gastroenterol 40(1):31-42, 1/2005. PMID: 15692787.
14. Rivera AA, Davydova J, Schierer S, Wang M, Krasnykh V, Yamamoto M, Curiel DT, Nettelbeck DM. Combining high selectivity of replication with fiber chimerism for effective adenoviral oncolysis of CAR-negative melanoma cells. Gene Ther 23(23):1694-702, 12/2004. PMID: 15496964.
15. Zinn KR, Szalai AJ, Stargel A, Krasnykh V, Chaudhuri TR. Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus. Gene Ther 11(19):1482-1486, 10/2004. PMID: 15295616.
16. Davydova J, Le LP, Gavrikova T, Wang M, Krasnykh V, Yamamoto M. Infectivity-enhanced cyclooxygenase-2-based conditionally replicative adenoviruses for esophageal adenocarcinoma. Cancer Res 64(12):4319-4327, 6/2004. PMID: 15205347.
17. Grandi P, Wang S, Schuback D, Krasnykh V, Spear M, Curiel DT, Manservigi R, Breakefield XO. HSV-1 virions engineered for specific binding to cell surface receptors. Mol Ther 9(3):419-427, 3/2004. PMID: 15006609.
18. Rivera AA, Wang M, Suzuki K, Uil TG, Krasnykh V, Curiel DT, Nettelbeck DM. Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo. Virology 320(1):121-134, 3/2004. PMID: 15003868.
19. Timares L, Douglas JT, Tillman BW, Krasnykh V, Curiel DT. Adenovirus-mediated gene delivery to dendritic cells. Methods Mol Biol 246:139-54, 2004. PMID: 14970589.
20. Korokhov N, Mikheeva G, Krendelshchikov A, Belousova N, Simonenko V, Krendelshchikova V, Pereboev A, Kotov A, Kotova O, Triozzi PL, Aldrich WA, Douglas JT, Lo KM, Banerjee PT, Gillies SD, Curiel DT, Krasnykh V. Targeting of adenovirus via genetic modification of the viral capsid combined with a protein bridge. J Virol 77(24):12931-12940, 12/2003. PMCID: PMC296051.
21. Belousova N, Korokhov N, Krendelshchikova V, Simonenko V, Mikheeva G, Triozzi PL, Aldrich WA, Banerjee PT, Gillies SD, Curiel DT, Krasnykh V. Genetically targeted adenovirus vector directed to CD40-expressing cells. J Virol 77(21):11367-11377, 11/2003. PMCID: PMC229360.
22. Yamamoto M, Davydova J, Wang M, Siegal GP, Krasnykh V, Vickers SM, Curiel DT. Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer. Gastroenterology 125(4):1203-1218, 10/2003. PMID: 14517802.
23. Takayama K, Reynolds PN, Short JJ, Kawakami Y, Adachi Y, Glasgow JN, Rots MG, Krasnykh V, Douglas JT, Curiel DT. A mosaic adenovirus possessing serotype Ad5 and serotype Ad3 knobs exhibits expanded tropism. Virology 309(2):282-293, 5/2003. PMID: 12758175.
24. Kim M, Sumerel LA, Belousova N, Lyons GR, Carey DE, Krasnykh V, Douglas JT. The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells. Br J Cancer 88(9):1411-1416, 5/2003. PMCID: PMC2741053.
25. Chaudhuri TR, Cao Z, Krasnykh VN, Stargel AV, Belousova N, Partridge EE, Zinn KR. Blood-based screening and light based imaging for the early detection and monitoring of ovarian cancer xenografts. Technol Cancer Res Treat 2(2):171-180, 4/2003. PMID: 12680799.
26. Pereboeva L, Komarova S, Mikheeva G, Krasnykh V, Curiel DT. Approaches to utilize mesenchymal progenitor cells as cellular vehicles. Stem Cells 21(4):389-404, 2003. PMID: 12832693.
27. Suzuki K, Fueyo J, Krasnykh VN, Reynolds PN, Curiel DT, Alemany R. A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 7(1):120-126, 1/2001. PMID: 11205899.
28. Dmitriev I, Kashentseva E, Rogers BE, Krasnykh VN, Curiel DT. Ectodomain of coxsackievirus and adenovirus receptor genetically fused to epidermal growth factor mediates adenovirus targeting to epidermal growth factor receptor-positive cells. J Virol 74(15):6875-6884, 8/2000. PMCID: PMC112205.
29. Bilbao G, Contreras JL, Zhang HG, Pike MJ, Overturf K, Mikheeva G, Krasnykh VN, Curiel DT. Adenovirus-mediated gene expression in vivo is enhanced by the antiapoptotic bcl-2 gene. J Virol 73(8):6992-7000, 8/1999. PMCID: PMC112785.
30. Douglas JT, Miller CR, Kim M, Dmitriev I, Mikheeva G, Krasnykh V, Curiel DT. A system for the propagation of adenoviral vectors with genetically modified receptor specificities. Nat Biotechnol 17(5):470-475, 5/1999. PMID: 10331807.
31. Bilbao G, Contreras JL, Gómez-Navarro J, Eckhoff DE, Mikheeva G, Krasnykh V, Hynes T, Thomas FT, Thomas JM, Curiel DT. Genetic modification of liver grafts with an adenoviral vector encoding the Bcl-2 gene improves organ preservation. Transplantation 67(6):775-783, 3/1999. PMID: 10199723.
32. Bilbao G, Contreras JL, Mikheeva G, Krasnykh V, Eckhoff DE, Thomas FT, Thomas J, Curiel DT. Genetic cytoprotection of human endothelial cells during preservation time with an adenoviral vector encoding the anti-apoptotic human Bcl-2 gene. Transplant Proc 31(1-2):1012-1015, Feb-Mar, 2/1999. PMID: 10083450.
33. Zinn KR, Douglas JT, Smyth CA, Liu HG, Wu Q, Krasnykh VN, Mountz JD, Curiel DT, Mountz JM. Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5). Gene Ther 5(6):798-808, 6/1998. PMID: 9747460.
34. Rosenfeld ME, Wang M, Siegal GP, Alvarez RD, Mikheeva G, Krasnykh V, Curiel DT. Adenoviral-mediated delivery of herpes simplex virus thymidine kinase results in tumor reduction and prolonged survival in a SCID mouse model of human ovarian carcinoma. J Mol Med (Berl) 74(8):455-462, 8/1996. PMID: 8872859.
35. Ganguly TC, Krasnykh V, Falany CN. Bacterial expression and kinetic characterization of the human monoamine-sulfating form of phenol sulfotransferase. Drug Metab Dispos 23(9):945-950, 9/1995. PMID: 8565785.
36. Blinov VM, Totmenin AV, Resenchuk SM, Olenina LV, Chizhikov VE, Kolykhalov AA, Gutorov VV, Pozdniakov SG, Krasnykh VN. Study of the structure-function organization of the variola virus genome. IV. Sequencing and analysis of the nucleotide sequence of the right terminus of the India-1967 strain genome. Mol Biol (Mosk) 29(4):772-789, Jul-Aug, 7/1995. PMID: 7476944.
37. Falany CN, Krasnykh VN, Falany JL. Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase. J Steroid Biochem Mol Biol 52(6):529-539, 6/1995. PMID: 7779757.
38. Degtyarev SKh Prikhod'ko EA, Rechkunova NI, Prikhod'ko GG, Krasnykh VN. Biochemical characterization of VspI methyltransferase. Gene 157(1-2):65-66, 5/1995. PMID: 7607528.
39. Falany JL, Krasnykh VN, Mikheeva G, Falany CN. Isolation and expression of an isoform of rat estrogen sulfotransferase. J Steroid Biochem Mol Biol 52(1):35-44, 1/1995. PMID: 7857871.
40. Yamakawa M, Krasnykh VN, Roy P. Phylogenetic relationships of the VP2 protein of a virulent isolate of bluetongue virus (BTV-23) compared to those of 6 other BTV serotypes. Virus Res. 34(1):81-92, 1994. PMID: 7831967.
41. Degtyarev SK , Prikhod'ko EA, Prikhod'ko GG, Krasnykh VN. Vspl methylase belongs to m6A-gamma class of adenine methylases. Nucleic Acids Res 21(8):2015, 4/1993. PMCID: PMC309450.
42. Krasnykh VN, Daniluk, NK, Iljichev, AA, Gorbunov, YA, Lomakin, AI, Sinyakov, AN, Vtorushina, IA, Yastrebov, SI, Popov, SG, Timofeev, IV, Shchelkunov, SN. Chemical-enzymatic synthesis and cloning of the Bacillus amyloliquefaciens a-amylase signal peptide for expression of the synthetic a2 human interferon gene. Biotechnologia 4:609-617, 1988.
43. Beklemishev AB, Golovin SI, Il'ichev AA, Mamaev LV, Krashykh VN. Expression in Escherichia coli cells of the nucleotide sequence of DNA coding for the bovine lipotropic hormone. Mol Gen Mikrobiol Virusol 10(10):19-23, 10/1987. PMID: 3323897.
44. Shchelkunov SN, Iljichev AA, Krasnykh VN, Timofeev IV, Ryazankin IA, Yamshchikov VF, Popov SG. Increasing the yield of interferon in Escherichia coli cells by using signal peptide constructions. Biotechnologia 3:146-151, 1987.
45. Gorbunov IU, Daniliuk NK, Il'ichev AA, Krashykh VN, Lomakin AI. Chemico-enzymatic synthesis of genetic elements for expression of synthetic genes in Bacillus subtilis cells. Bioorg Khim 12(5):647-654, 5/1986. PMID: 3089232.

Abstracts

1. Belousova N, Mikheeva G, Xiong C, Soghomonyan S, Bidaut L, Li C, Gelovani J, Krasnykh V. Development of targeted gene vectors for tumor imaging based on simian adenovirus serotype 24. World Molecular Imaging Congress, Kyoto, Japan, 2010.
2. Belousova N, Mikheeva G, Xiong C, Soghomonyan S, Bidaut L, Li C, Gelovani J, Krasnykh V. Development of Targeted Gene Vectors for Tumor Imaging Based on Simian Adenovirus Serotype 24. World Molecular Imaging Congress, Kyoto, Japan, 2010.
3. Mikheeva G, Belousova N, Krasnykh V. The knob domain replacement strategy is broadly applicable to a wide variety of adenovirus fiber proteins. The 13th Annual Meeting of American Society of Gene Therapy, Washington, DC, 2010.
4. Dreier B, Hess C, Boczek E, Krasnykh V, Pluckthun A. Affinity maturation of DARPins for efficient adenoviral gene transfer. VIII European Symposium of The Protein Society, Zurich, Switzerland, 2009.
5. Mikheeva G, Derier B, Hess C, Boczek E, Belousova N, Pluckthun A, Krasnykh V. Design of bi-specific DARPin-derived adapters for targeting of adenovirus vectors. The 12th Annual Meeting of American Society of Gene Therapy, San Diego, CA, 2009.
6. Mikheeva G, Belousova N, Krasnykh V. Development of tumor-targeted vectors derived from simian adenovirus. The 11th Annual Meeting of American Society of Gene Therapy, Boston, MA, 2008.
7. Belousova N, Kojanyan M, Mikheeva G, Krasnykh V. Design and characterization of Her2-targeted adenovirus vectors. The 10th Annual Meeting of the American Society of Gene Therapy, Seattle, WA, 2007.
8. Belousova N, Mikheeva G, Krasnykh V. Targeting of Ad5 vectors using designed protein ligands. Annual Meeting of European Society of Gene and Cell Therapy, Rotterdam, The Netherlands. 2007.

Book Chapters

1. Timares L, Douglas JT, Tillman BW, Krasnykh V, and Curiel, DT. Adenovirus-mediated gene delivery to dendritic cells. In: Gene Delivery to Mammalian Cells. 2, 139-154, 2004.
2. Krasnykh V and Douglas JT. Targeted adenoviral vectors I: Transductional targeting. In: Adenoviral Vectors for Gene Therapy. Ed(s) Curiel DT and Douglas JT. Academic Press: San Diego, 2002.

Grant & Contract Support

Title: Novel near-infrared fluorescence imaging probes for intraoperative tumor detection
Funding Source: MD Anderson IRG program
Role: Principal Investigator
Duration: 10/1/2014 - 11/15/2016
 
Title: New generation of radiotracers for PET imaging of molecular signatures of tumors
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 8/7/2014 - 7/31/2017

Last updated: 8/10/2016