Sandra Quackenbush

Last updated
Sandra Quackenbush
EducationBiology: Animal Science Nutrition, Ohio State University, 1979, Retroviral Pathogenesis, Colorado State University, 1987, Retroviral Pathogenesis, Colorado State University, 1994
Alma materOhio State University (BA) Colorado State University (MA), (Ph.D)
Known forResearch of Walleye Dermal Sarcoma Virus and Feline Leukemia Virus
Scientific career
FieldsBiology, Virology
InstitutionsColorado State University

Sandra L. Quackenbush is an American virologist working as the associate dean of academic and student affairs and professor of retrovirology at the Colorado State University College of Veterinary Medicine and Biomedical Science. Her research interests include viral pathogenesis, with emphasis in viral-induced oncogenesis. [1]

Contents

Education

Sandra Quackenbush received her bachelor's degree in animal science nutrition from Ohio State University in 1979, obtained her Masters in retroviral pathogenesis from Colorado State University in 1987 and her Ph.D. also in retroviral pathogenesis in 1994 from Colorado State University. She has had several articles published within her field of study. [1]

Research contributions

Summary of work

Quackenbush has worked with both gammaretrovirus (feline leukemia virus) and epsilonretrovirus (walleye dermal sarcoma virus) extensively. Gammaretroviruses are single stranded RNA viruses that are present in the genome of vertebrates including reptiles, birds, amphibians, and mammals. [2] Epsilonretroviruses are viruses that infect fish, and have a single stranded RNA genome. [3] Retroviruses within these genera cause disease by containing RNA sequences that code for proteins that promote oncogenesis which leads to sarcomas and leukemias. [4] Through her work with two genera of retroviruses, Quackenbush determined mutations to Gammaretrovirus (feline leukemia virus) makes them less lethal, and Epsilretrovirus (walleye dermal sarcoma virus) contains sequences that encode for cyclin proteins, leading to the proliferation of normal cells and eventually giving a means for cancer cells to become abundant [5] [6]

Most notable work

Her most notable work focuses on feline leukemia virus. This report was published in Science in 1988 and has been cited over 200 times. The research found that replication-defective strains of feline leukemia virus can cause deadly immunodeficiency syndrome in felines. Results of the study revealed that a less fatal form of immunodeficiency syndrome could be induced with mutations to the feline leukemia virus. [6]

Phylogeny of Retroviruses Phylogeny of Retroviruses.svg
Phylogeny of Retroviruses

Most recent publication

The most recent published study Quackenbush was involved in was the study of walleye dermal sarcoma virus. This research investigated the role of retroviral cyclin (RV-cyclin) in sarcoma progression in walleyes as a comparable study to human cancer. It was determined that he RV-cyclin bound to cyclin-dependent kinase 8 (CDK8) and increased its activity. The genes IEGs are normally stimulated for transcription by cyclin C with an up regulation in CDK8 IEGs are expressed at a higher rate for a period of time. Since IEGs encode for cell proliferation a mutation in the CDK8 could lead to dermal sarcoma. This investigation determined the mechanism behind retrovirus-induced oncogenesis caused by walleye dermal sarcoma virus. These implications would later be used to determine other retroviral-induced oncogenesis in human cancers. [5]

Current research

Quackenbush has current laboratory research focusing on viral-induced oncogenesis, in fish retroviruses. Studies investigate how a virus (walleye dermal sarcoma virus) is involved in the introduction of sarcomas. Her lab is trying to determine the mode by which transcription, apoptosis, and transduction are controlled by viral regulatory proteins such as kinases. [1] Studies focus on the walleye dermal sarcoma virus and inducing sarcomas.

Publications

Honors

See also

Related Research Articles

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Kaposi's sarcoma-associated herpesvirus</span> Species of virus

Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses. Even after many years since the discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

<i>Gammaretrovirus</i> Genus of viruses

Gammaretrovirus is a genus in the Retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds.

Rous sarcoma virus (RSV) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

<span class="mw-page-title-main">Viral transformation</span>

Viral transformation is the change in growth, phenotype, or indefinite reproduction of cells caused by the introduction of inheritable material. Through this process, a virus causes harmful transformations of an in vivo cell or cell culture. The term can also be understood as DNA transfection using a viral vector.

<span class="mw-page-title-main">Seliciclib</span> Chemical compound

Seliciclib is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growth phase or state within the cell cycle of treated cells. Seliciclib is being developed by Cyclacel.This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study.

<span class="mw-page-title-main">Long terminal repeat</span>

A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.

The gag-onc fusion protein is a general term for a fusion protein formed from a group-specific antigen ('gag') gene and that of an oncogene ('onc'), a gene that plays a role in the development of a cancer. The name is also written as Gag-v-Onc, with "v" indicating that the Onc sequence resides in a viral genome. Onc is a generic placeholder for a given specific oncogene, such as C-jun..

Env is a viral gene that encodes the protein forming the viral envelope. The expression of the env gene enables retroviruses to target and attach to specific cell types, and to infiltrate the target cell membrane.

<span class="mw-page-title-main">Cyclin-dependent kinase 9</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

<span class="mw-page-title-main">Cyclin T1</span> Protein-coding gene in humans

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.

<span class="mw-page-title-main">Cyclin B1</span> Protein-coding gene in the species Homo sapiens

G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene.

<span class="mw-page-title-main">MNAT1</span> Protein-coding gene in the species Homo sapiens

CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.

<span class="mw-page-title-main">Tyrosine-protein kinase Fes/Fps</span> Human protein and coding gene

Tyrosine-protein kinase Fes/Fps also known as proto-oncogene c-Fes/Fps is an enzyme that in humans is encoded by the FES gene. FES was originally cloned as a retroviral oncogene from feline (v-FES) and avian (v-FPS) sarcomas. This triggered the subsequent identification and cloning of the cellular FES (c-FES) genes in birds and mammals.

The walleye epidermal hyperplasia viruses are two species of retroviruses classified under Epsilonretrovirus, a genus in the family of Retroviridae. There are three genome sequenced and identified exogenous retroviruses of this genus which include two known types associated with walleye epidermal hyperplasia disease. Both viral types are confirmed to be the causative agents of the neoplastic condition in the freshwater fish species, the North American walleye (Sander vitreus). The specific association of retroviral infection with proliferative lesions in fish is based on the presence of retrovirus-like particles and reverse transcriptase activity from neoplastic tissue. Although both virus types have been observed in lesions of diseased fish, each cell of the infected tissue is host to a specific virus. Transmission studies have also shown that WEHV-2 has been the more proliferative agent of the condition as compared to WEHV-1.

Retroviral matrix proteins are components of envelope-associated capsids of retroviruses. These proteins line the inner surface of viral envelopes and are associated with viral membranes.

<span class="mw-page-title-main">Dinaciclib</span> Chemical compound

Dinaciclib (SCH-727965) is an experimental drug that inhibits cyclin-dependent kinases (CDKs). It is being evaluated in clinical trials for various cancer indications.

Gibbon-ape leukemia virus (GaLV) is an oncogenic, type C retrovirus that has been isolated from primate neoplasms, including the white-handed gibbon and woolly monkey. The virus was identified as the etiological agent of hematopoietic neoplasms, leukemias, and immune deficiencies within gibbons in 1971, during the epidemic of the late 1960s and early 1970s. Epidemiological research into the origins of GaLV has developed two hypotheses for the virus' emergence. These include cross-species transmission of the retrovirus present within a species of East Asian rodent or bat, and the inoculation or blood transfusion of a MbRV-related virus into captured gibbons populations housed at medical research institutions. The virus was subsequently identified in captive gibbon populations in Thailand, the US and Bermuda.

The Walleye dermal sarcoma virus (WDSV) is a retrovirus that infects walleye often causing oncogenesis. WDSV is an exogenous retrovirus belonging to the subfamily Orthoretrovirinae. This virus is related to the walleye epidermal hyperplasia viruses type 1 and type 2, all belonging to the epsilonretrovirus genus based on similarities of the gene coding for the reverse transcriptase conserved in retroviruses.

References

  1. 1 2 3 NA. "Sandra L Quackenbush". College of Veterinary Medicine & Biomedical Sciences. Colorado State University. Retrieved 1 May 2015.
  2. NA. "Gammaretrovirus". Right Diagnosis from healthgrades. Health Grades Inc. Retrieved 19 May 2015.
  3. NA. "Epsilonretrovirus". ViralZone. Swiss Institute of Bioinformatics. Retrieved 19 May 2015.
  4. H, Robinson (1982). "Retroviruses and cancer". Reviews of Infectious Diseases. 4 (5): 1015–1025. doi:10.1093/clinids/4.5.1015. PMID   6755614.
  5. 1 2 Birkenheuer, C; Brewster, C; Quackenbush, S; Rovnak, J (2015). "Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitation". American Society for Microbiology. 89 (10): 5450–5461. doi:10.1128/JVI.00464-15. PMC   4442519 . PMID   25741012.
  6. 1 2 Overbaugh, J; Donahue, PR; Quackenbush, SL; Hoover, EA; Mullins, JI (1988). "Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats". Science. 239 (4842): 906–910. doi:10.1126/science.2893454. PMID   2893454.
  7. Brewster, CD; Bikenheuer, CH; Vogt, MB; Quackenbush, SL; Rovnak, SL (2011). "The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8". Virology. 409 (2): 299–307. doi:10.1016/j.virol.2010.10.022. PMC   3008307 . PMID   21067790.
  8. Paul, TA; Rovnak, J; Quackenbush, SL; Whitlock, K; Zhan, H; Gong, Z; Spitsbergen, J; Bowser, PR; Casey, JW (2010). "Transgeneic expression of walleye dermal sarcoma virus rv-cyclin (orf A) in Zebrafish does not result in tissue proliferation". Marine Biotechnology. 13 (2): 142–150. doi:10.1007/s10126-010-9274-2. PMC   3364296 . PMID   20349325.
  9. Quckenbush, SL; Casey, JW; Bowser, PR; Rovnak, J (2010). "Cancers Induced by Piscine Retroviruses". Retroviruses and Insights into Cancer. pp. 191–218. doi:10.1007/978-0-387-09581-3_7. ISBN   978-0-387-09580-6.
  10. Eiden, MV; Radke, K; Rovnak, J; Quackenbush, SL (2010). Non-primate mammalian and fish retroviruses. NYC: Caister Academic Press.
  11. University Relations. "Five KU faculty named outstanding educators". OREAD. The University of Kansas. Retrieved 13 May 2015.