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Click on each name to see what type of research integrase research he or she is conducting!!

Many of these topics are still undergoing research in the Lab

 

Dr. Samson Chow

I have no idea what Dr. Samson Chow does. All I know is that its very very very important =O.

 

 

 

 

 

 

Dr. Thomas Wilkinson

hiv_rt- HIV-1 Reverse Transcriptase

Dr. Wilkinson is currently exploring the role of integrase as a cofactor for the reverse transcription process in HIV.  He conducts structural, biochemical, and genetic studies of HIV-1 integrase-reverse transcriptase interactions in vitro and in tissue culture. 

As a second project, Dr. Wilkinson is also studying the underlying principles for integrase-target DNA recognition.  He employs molecular modeling to predict HIV integrase mutations that may lead to altered DNA specificity, and then test these mutant proteins for their actual DNA sequence selectivity using integrase activity assays.  The information gained from this research can potentially guide development of safer lentiviral vectors for gene therapy applications.

 

Dr. Cora Woodward

nucleoporin- NPC Complex

Dr. Woodward's research focuses on the lentiviruses' capability to penetrate the nuclear envelope to get into the nucleus. Looking specifically at the lentivirus HIV's integrase protein, Dr. Woodward is investigating the links between integrase and the nucleopore complex.

The nucleopore complex is comprised of over 30 different proteins, each having a specific role in the transport of molecules into and out of the nucleus. What is known is that large viral Pre-Integration Complexes and other viral proteins are able to go through the nuclear envelope into the nucleus via the nucleopores, however this mechanism is uknown. It is worth noting that the Pre-Integration Complexes that are able to enter the nucleus appear to be physically larger than the nucleopore complex itself. The viral protein integrase is also known to be involved in nuclear import. Integrase has been shown to have karyophilic properties, and thus is an interesting topic for research.

Part of the research involves characterizing the karyophilic properties of integrase and investigating the reactions that take place in order for integrase to enter the nucleus. Integrase is shown to have a different type of nuclear import than most proteins or molecules. Integrase has also been shown to be in close association with the PIC and is vital to viral transfection. Thus it is important to find out exactly what mechanisms integrase uses in order to react with nucleopore proteins to breach the nuclear envelope. Dr. Woodward believes that the nucleopore protein NUP 153 may be associated with the nuclear import of integrase.

NUP 153 has 3 different domains, one of which is a C-Terminal domain which is of much interest. NUP 153 has two different states. In the active states, the C terminal changes into a configuration in which it is elongated, and sometimes sticks out into the cytoplasm. In the deactive state, the C terminal shrinks and collapses on itself. It is the reaction between the C terminal in its active state and integrase that carries the weight of the research. Dr. Woodward believes that the C terminal domain of NUP 153 reacts with integrase and could possibly have a role in the nuclear import of integrase.

Image courtesy of: Birthe Fahrenkrog1 & Ueli Aebi.

Nature Reviews Molecular Cell Biology 4, 757-766 (October 2003) | doi:10.1038/nrm1230

 

Kunkai Su

integrase1- Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator

Kunkai's research deals with the integration of viral cDNA into the hosts' genome. Because an essential step in the cycle of viral life is to successfully integrate its own cDNA into the host, retroviruses have become a popular mechanism for gene delivery or therapy. However, the nonspecific nature of retroviral DNA interation presents dangers and hazards in the possible variation of gene expression found in the host. Thus it is important that a safe and reliable way is found to integrate DNA into specific, controlled sites.

Because integrase is an essential protein for viral cDNA integration, wild type HIV-1 integrase was prepared and fused with the E2C protein. The E2C protein recognizes and binds to a specific 18 base pair site on DNA. The integrase was successfully fused onto the zing finger domain of E2C and thus the fusion integrase-E2C protein was created. This fusion protein recognizes and delivers its DNA into specific sites determined by the E2C binding. The very specific nature of the base pair recognition created an efficient and versitile framework for directing foreign DNA into a predetermined DNA site.

Image courtesy of: Cherepanov P, Ambrosio AL, Rahman S, Ellenberger T, Engelman A. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17543-4.

Marisa Briones

viral_core-HIV virus with the inner viral core

Marisa's project focuses on the role HIV integrase (IN) plays in an early
event in the replication cycle of HIV, during uncoating of the viral
core.

After fusion with the plasma membrane, the viral core is
released into the cytoplasm, where it must uncoat, resulting in the
disassembly of the capsid (CA) protein from the ribonucleoprotein
complex. Uncoating is an important step and changes in core stability
can have deleterious effects on uncoating, resulting in defects in
downstream steps including reverse transcription and nuclear entry.
By isolating cores from IN mutant viruses and comparing to wildtype,
we have found that mutations in IN result in defects in core
stability. Currently, we are investigating the molecular mechanisms
underlying these uncoating defects in the IN mutants.

Image courtesy of: DK images

 

Alice
Not Updated Yet.
Serena Lee

 

Serena’s field of research deals with the xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus detected in 40% of the prostate cancer patients homozygous for the R462Q variant.

One of Serena’s projects is to study XMRV’s molecular mechanism in prostate cancer formation. Retroviruses are capable of inducing tumors in their host animals by a phenomenon called proviral insertional mutagenesis. The insertion of a retroviral genome into the host cell chromosome may act as a promoter or enhancer of a proto-oncogene, inducing tumor formation within the tissue. Serena is currently doing further research on sequencing and mapping XMRV integration sites in human prostate cancer cells with defective and functional RNase L. She is also analyzing additional XMRV integration sites from prostate cancer patients homozygous for R462Q RNase L variant to determine the integration site preference of XMRV and the effects of its insertion. Serena’s other project is to establish a mouse model that will be used to dissect XMRV’s role in cancer formation.  This study will further dissect XMRV’s role in prostate cancer development and ultimately help identify viral targets for cancer prevention and treatment.

 

Jonathan Wu
Jonathan's responsibilities in the lab include designing the website as well as maintaining the lab website. Jonathan conducts research on the nucleopore complex as well.

 

 

cool_sites

Research could not be possible without the support of these institutions:

ucla pharmacology- UCLA pharmacology Website

 

ucla website- UCLA main website

 

access- UCLA access website

 

jonsson comp

-UCLA Jonsson Comprehensive Cancer Center

 

ucla aids- UCLA Aids Institute