Student Project description:
Predicting response to taxanes: molecular characterization and functional assessment of microtubule associated proteins as prognostic and predictive markers in breast cancer.
Current breast cancer therapy involves the use of taxanes such as docetaxel and paclitaxel.  These potent chemotherapeutic agents exhibit highly variable response rates indicating the need for a diagnostic assay that can differentiate responders from nonresponders.  My work involves the molecular and functional characterization of microtubule associated proteins as prognostic and/or predictive markers of taxane sensitivity in order to accurately select patients for taxane therapy.

Student Project description:
A Novel Oncogenic Role for the KSHV Protein K5
Kaposi’s Sarcoma Associated Herpesvirus (KSHV) is a gamma-2-herpesvirus that accounts for a large percentage of virally caused cancers worldwide making it a considerable public health burden. However, considering the majority of KSHV infection is asymptomatic, the final switch that drives KSHV latent infections to the pathological KS (Kaposi Sarcoma) has been elusive. We’ve recently discovered that KSHV– K5 expressing monocytes have faster growth rates, increased total phospho-tyrosine and phospho-Akt levels. The cells also have increased glycolysis showing an altered metabolism, a hallmark of metastatic  transformation also dubbed as the Warburg Effect. These phenotypes are serum dependent implicating an altered kinetic of growth factor signaling rather than a de novo signaling being initiated by K5. We’re currently exploring the contributions of K5 in altering growth factor signaling pathways and the subsequent role of K5 in KSHV driven oncogenesis. We believe that this understanding of molecular mechanism of K5 functionality will be crucial to elimination of KSHV driven cancers and contribute to our understanding of both viral and non-viral oncogenic mechanisms.

Student Project description:
"Functional Role of Met in the Nucleus"
The Met receptor is a transmembrane receptor tyrosine kinase that when activated signals through a number of pathways essential for cell spreading, cell-cell dissociation, and increased motility. Previous work in our lab has shown that like a number of other membrane-bound RTKs, Met can localize to the nucleus. We have also demonstrated that high levels of nuclear Met are associated with poor survival. The aim of my research is to determine the function of nuclear Met and how it is contributing to cancer progression.

Student Project description:
Signaling by the NRG1 ICD
NRG1 is a ligand for the ErbB receptor family and is essential for development due to its involvement in the cardiac and nervous systems. NRG1 is also involved in signaling in the mammary gland that occurs during pregnancy and lactation. NRG1 is expressed on the cell surface as a transmembrane protein. The extracellular domain is released by cleavage and acts as the ligand for the receptors ErbB3 and ErbB4. Interestingly, the NRG1 intracellular domain is extremely large compared to other ErbB ligands and is evolutionarily conserved. My project investigates potential functions of this conserved intracellular region. 

Student Project description:
Characterization of a Vesicular Stomatitis Virus Based HBV Vaccine Vector
The goal of my project is to develop a novel prophylactic and therapeutic vaccine for hepatitis B virus (HBV). I am proposing that one potential attractive alternative to the current HBV vaccine may be a recombinant vesicular stomatitis virus (VSV)-based HBV vaccine. In addition to inducing protective immune responses against a variety of pathogens after a single dose, VSV-based vaccines are also showing promise as treatments for chronic viral infections.  Through my work, I hope to provide evidence that a VSV-based HBV vaccine may not only make an improved prophylactic vaccine, providing long-term immunity in a single dose, but that it may also be an effective therapy for chronic HBV infection.

Student Project description:
Thrombospondin 2 in wound healing
Thrombospondin 2 (TSP2) is an anti-angiogenic extracellular matrix protein, known to modulate cell-ECM interactions.  TSP2 knockout mice have altered collagen fibrillogenesis and enhanced wound healing in ischemia and angiogenesis models.  Improved healing is associated with enhanced angiogeneisis, through mechanisms including altered ECM assembly, MMP expression and altered receptor mediated signaling.  The goals of this project aim to understand the significance of these components to vascular remodeling, particularly in the context of wound healing.

Student Project description:
Quantitative measurement of Estrogen Receptor (ER) to improve its prognostic and predictive value in breast cancer
My research is inspired by the current clinical problems surrounding the use of Estrogen Receptor (ER) to determine patient prognosis and predict response to endocrine therapies.  Part of my work has focused on developing ways to improve standardization & quantification of ER in the clinical setting, and using these to examine the degree of, and causes for, the misclassification that currently happens.  I am also interested in all of the recent biological evidence for the existence and importance of ER (and its isoforms) outside the nucleus, and the role this non-genomic signaling plays in promoting pathways of cellular survival and proliferation in response to Tamoxifen.  My project aims to help translate these biological advancements to the clinic by developing assays that can detect the functional presence of non-genomic ER signaling or ER isoforms in breast cancer, and using these to improve the way we predict response to antiestrogen therapies, especially Tamoxifen.

Student Project description:
Mechanism of the Nuclear Localization of c-Met
The Met receptor tyrosine kinase for the hepatocyte growth factor (HGF) plays a critical role in cancer cell proliferation, motility, invasion and metastasis. Our lab has found tthat high expression of Met in the nucleus is associated with shorter survival in breast cancer. Furthermore, we have found a 60 kD fragment that localizes to the nucleus. My project aims to identify the proteins and pathways involved in this process with the underlying hypothesis that Met in the nucleus is playing an important role in cancer. Since several pharmaceutical companies are actively investigating Met inhibitor based therapies for cancer, a more complete understanding of the mechanism and function of Met in the nucleus is essential.

Student Project description:
Determining the role of RAD18 in the Fanconi anemia Pathway
Fanconi anemia (FA) is a rare genetic disorder characterized by congenital abnormalities, bone marrow failure, and an increased susceptibility to cancer and leukemia.  Thirteen FA genes have been cloned whose products are thought to function in a common pathway involved in DNA repair.  Central to this pathway is the monoubiquitylation and chromatin localization of two FA proteins, FANCD2 and FANCI.  We have identified novel components of FANCD2-containing protein complexes through chromatographic purification, such as the E3 ubiquitin ligase RAD18 as well as other known repair proteins.  The objective of my research is to define the role of these proteins in regulation of the FA pathway.

Student Project description:
Defining the interaction between the Fanconi anemia pathway and the transcriptional machinery/RNA
anconi anemia(FA) is an autosomal and X-linked recessive disorder caused bybiallelic mutation of one of the 13 genes which make up the FA pathway. Cells from patients with FA exhibit hypersensitivity to DNA crosslinking agents and gross chromosomal abnormalities such as radial chromosomes and translocations. As the result of these characteristics, FA has been categorized as a disease of genomic instability and the FA pathway has been hypothesized to function in DNA repair.  While the interaction of several FA proteins with proteins known to participate in the homologous recombination and translesion synthesis methods of DNA repair has lent credibility to this hypothesis, there are several lines of evidence which link the FA pathway to RNA metabolism and the transcriptional machinery as well.  As aberrant processing of nascent RNA transcripts produced by the transcriptional machinery can result in genomic instability, a role for the FA protein FANCD2 in sensing DNA damage encountered by transcribing polymerases and in signaling for transcription termination fits well with the hypothesized function of the pathway.  My project involves defining the interaction of the FA pathway and more specifically FANCD2 with the transcriptional machinery and RNA.

Student Project description:
Multiplexed Assessment of HER2 pathway proteins to predict response to Trastuzumab
My project aim is to quantify the level of expression and subcellular localization of HER2 pathway proteins and use the information to predict response and resistance of Trastuzumab. Through this project, I intend 1) to classify HER2 positive breast cancer into more detailed sub-types; 2) to find clinical implication of complicated Trastuzumab resistance; 3) to find a model that will assist the determination of Trastuzumab administration.

Student Project description:
Exploring Receptor Tyrosine Kinase Activation in Melanoma
Receptor tyrosine kinases (RTKs) are proteins located at the cell surface which control cell differentiation, proliferation, and survival.  RTKs are frequently dysregulated in cancer, which makes them viable targets for therapeutic intervention.  Development of RTK-directed therapies has, however, been limited by a lack of information about which RTKs are active in specific cancer subtypes, how these activations are occurring, and how the signaling of one RTK may compensate for the signaling of another RTK.  My project explores the activation of RTKs in melanoma and whether these activations occur in specific patterns.  The project’s goal is to determine which RTKs have the greatest influence on melanoma pathogenesis and how these RTKs should be targeted to modulate disease progression. 

Student Project description:
Thrombospondin-2 in vascular pathology
Thrombospondin 2 (TSP2) is a matricellular protein that modulates cell-matrix interactions and is a potent inhibitor of angiogenesis during tissue repair. Previous studies in TSP2-null mice showed enhanced wound healing, increased angiogenesis, and altered collagen fibrillogenesis suggesting that TSP2 regulates several cellular processes during repair. In addition, preliminary evidence suggests of a potential negative feedback mechanism between TSP2 and nitric oxide (NO). Moreover, there seems to be a correlation between the negative outcome of tissue repair in the presence of low NO levels and the presence of increased TSP2. Interestingly, patients with Diabetes Mellitus type I and II are unable to heal wounds efficiently and this pathology is associated with reduced angiogenesis, altered extracellular matrix (ECM) deposition and remodeling, and a decrease in the levels of NO. The main goal of this project is to investigate the hypothesis that increased TSP2 expression in diabetic wounds, due to low NO levels, contributes to vascular pathology leading to compromised healing.

Student Project description:
Bmx in angiogenesis and lymphangiogenesis
Both angiogenesis and lymphangiogenesis are important for tumor metastasis. Our lab have identified a TNFR2-Bmx kinase (bone marrow tyrosine kinase in X chromosome) angiogenic pathway, which plays a critical role in ischemic-induced angiogenesis. My project involves characterization of the in vivo function of Bmx in angiogenesis and lymphangiogenesis, as well as its significance in tumor metastasis to distant organs.

Student Project description:
Characterization of the features of early stage breast cancers using in vivo propagation of human breast tissue
Much of the study of breast cancer tumorigenesis has been conducted using immortalized cell lines, some of which are derived from metastases, and not primary tumors, thus limiting the application of the results from these studies. Therefore, there is a need to develop an alternate source of material to be used in breast cancer research.  In my project, I plan to use mice to expand and propagate human breast tissue, both normal and tumorigenic, grown initially as mammospheres following isolation. This approach can also be used to determine the functional characteristics of the mammospheres, in terms of reconstituting ability (“stemness”), as well as the effects of the stromal microenvironment on different classes of tumors/mammospheres.  This work will be done in collaboration with Seema Agarwal in the Rimm lab.  A second, and related project involves the use of genomic and transcriptional analyses to determine molecular features of early stage DCIS lesions that may predict progression to invasive breast cancer.

Student Project description:
Characterization of the Histone Demethylase PLU-1
Recent studies have shown the importance of histone methylation in the regulation of target gene expression. My project involves characterizing roles of the histone demethylase PLU-1 in the human breast cancer. Another focus of the study is to determine whether PLU-1 would act as a mechanism for Herceptin resistance observed in breast cancer cells.

Student Project description:

Student Project description:
Significance of Progesterone Receptor Isoforms Alpha and Beta in Breast Cancer
Levels of progesterone and estrogen receptors are routinely assessed in breast cancer patients to aid in diagnosis and prediction of response to endocrine therapy. There are two isoforms of progesterone receptor, alpha and beta. Little is known about the significance of the relative levels of the receptor isoforms so the current aim of my research is to quantify levels of progesterone receptor isoforms in large breast cancer cohorts to assess their value as prognostic and/or predictive factors for breast cancer.