Research

I am molecular cancer biologist with training in translational medicinal research focusing on genomics and epigenomics of drug-resistance in gynecological cancers. The approaches I used covers whole (epi)genomics (transcriptomics, Methylation, copy number alterations and NGS) analysis of primary patient material and performing functional validation in patient-derived or established cell lines and xenograft (PDX) models.

Currently, I am involved in research project of targeting cancer stem cells in breast cancer using novel therapeutic approaches like antibody-drug conjugate to overcome drug resistance and reoccurrence. In parallel to my current research projects, I have a keen interest to implement current (epi)genomics knowledge in targeting tumor microenvironment (including immune system) to treat cancer or overcome drug-resistance problem.

Targeting cancer stem cells in breast cancer using antibody-drug conjugates (2016-present)

This project is in partnership with biopharmaceutical company Synthon. The major aim of this project is to study the efficacy of antibody-drug conjugates in different breast cancer models (2D, 3D and in vivo) and its mechanisms

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Identification of novel DNA methylation markers in relation to platinum-based chemotherapy in ovarian cancer (2011-2015)

We took a genome-wide integrated epigenomics approach to identify novel DNA methylation markers in relation to platinum-based chemotherapy in ovarian cancer. Further markers were validated on independent patient cohort and established in vitro and in vivo models. Moreover, Functional validation will also be done to dig the biological relevance of identified markers...

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Epigenomic characterization of ovarian cancer Patient-derived xenograft (PDX) mouse model

In this study, we compared the DNA methylome of primary tumors from HGSOC patients with their corresponding PDXs to determine their epigenomic stability among generations using genome-wide methylation arrays. Aims of this study were a) to explore how representative HGSOC PDXs are for their corresponding primary the tumors' methylome and b) to evaluate the effect of epigenetic therapy and cisplatin on putative epigenetically regulated genes and their related pathways...

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Establishment of Patient-derived xenograft (PDX) mouse model for ovarian cancer for investigating tumor biology and performing preclinical drug testing experiments (2011-2015)

We established the facility for PDX mouse model of ovarian cancer. Currently, we have all histological sub-type of ovarian cancer as PDX mouse model which are immunohistochemically and genomically validated. We are investigating the tumor biology using OMICS approach with the help of these PDX model and performing pre-clinical drug testing of novel (chemo)therapeutics or their combinations...

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Platinum-chemoresponse markers for high grade serous ovarian cancer (HGSOC) patients (2011-2013)

We investigated the activation status of the DNA damage repair pathway (DDR) components in HGSOC for finding novel predictive marker for platinum-based chemotherapy. For assessment of expression and activation status various DDR components in HGSOC patients, we performed immunohistochemistry on TMAs of large cohort of pre-therapy advanced stage HGSOC patients and correlated them with clinicopathological characteristics. Further, to get mot insight into the biological basis of novel markers, we performed genes knock-in and knock-out in-vitro experiments in various representative ovarian cancer cell lines and their effect on chemoresponsiveness...

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Targeting of interferon-gamma to tumor stromal fibroblasts using a PDGF receptor-recognizing carrierv (2010-2011)

In this study, we targeted to block the function of tumor stromal cells such as cancer-associated fibroblasts and pericytes is an emerging field in cancer therapeutics as these cells play a crucial role in promoting angiogenesis and tumor growth via paracrine signals. We delivered IFNγ to stromal fibroblasts and pericytes, considering its direct anti-fibrotic activity, using our Platelet-Derived Growth Factor-beta Receptor (PDGFβR)-binding carrier (pPB-HSA), as these cells abundantly express PDGFβR. We chemically conjugated IFNγ to pPB-HSA using a heterobifunctional PEG linker and studied in vitro and in vivo anti-angiogenetic and anti-tumor effects of this tumor stromal compartment-targeted conjugate...

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Investigate the molecular mechanism of high fat diet-induced renal endothelial dysfunction in humanized-CRP transgenic mice (2010)

In this research project, we studied Endothelial dysfunction which is an early predictive marker for atherogenic cardiac complications and a common mechanistic link between cardiovascular disease (CVD) and chronic kidney disease (CKD) in metabolic syndrome (MS). Since C-reactive protein (CRP), a inflammatory marker, plays a crucial role in inflammatory diseases progression, therefore, human CRP transgenic mouse model (hCRPtg) with human CRP transgene was developed to study role of CRP in inflammatory processes. In this study, we investigated the effect of high fat diet (HFD) on the renal endothelial dysfunction in hCRPtg male mice and analyzed metabolic and renal-pathophysiological changes in the kidneys of HFD hCRPtg mice in comparison to normal chow mice. In addition, we also studied effects of anti-hyperlipidemic (rosuvastatin) and anti-diabetic (rosiglitazone) drugs in these hCRPtg mice.