Day 1 :
Unichem Laboratories Ltd, India
Time : 9:30-10:15
Dr Sudeep Kumar did his Post Doc in Biotech from Valencia, Spain on purification, cloning and sequencing of Cellulase and Xylanase enzyme. He has more than 20 years of experience in Biopharma. He has worked from R&D to tech transfer and manufacturing of different molecules. He is dealing with different regulatory agencies for approval and faced WHO, USFDA and other regulatory audits. He also actively involved with clinical research team for Preclinical and clinical trials of recombinant proteins and vaccine. He established the VLP technology platform for different vaccine in India in collaboration with Novavax.
Recombinant protein (ULLB-0005), is derived from a natural fungal protein, which has high binding specificity toward the carbohydrate antigen (Galβ1–3GalNAc-α-O-Ser/Thr). The natural Amino acid sequence has been modified to make more stable and soluble protein. Modified sequence has been cloned and express in E.coli. The protein was purified through different column chromatography and was characterized as a single protein.
The present study evaluated the anticancer activity of Recombinant protein ULLB-0005 by determining in vitro cytotoxicity fingerprint, efficacy, mechanism and safety in human cell lines. Promising cytotoxicity was observed in 9 different cancer cell line, with a good safety profile in human PBMCs. The efficacy of the Molecule as antitumor agent was assessed in respective xenograft immuno-compromised mice models in vivo. As expected the molecule showed strong anti-cancer activity in immune-compromised mice model in various cancers which was observed in the reduction of tumor volume.
ULLB-0005 induced strong apoptotic signal by modulating Phosphatidyl serine (PS) externalization, mitochondrial membrane depolarization, cell cycle arrest, ultimately leading to death in cancer cells. Inhibition of proliferation and migration was observed in human endothelial cells, suggesting potential antiangiogenic effect.
Further studies to evaluate possible synergistic effect of the molecule with approved chemotherapeutic agents for Breast and Pancreatic cancers showed good synergy in In-vitro test. Detailed multi-arm mechanistic studies to investigate the effect of the molecule on multiple targets and signaling pathways involving kinases, GPCRs, Growth factor receptors, inflammatory markers and circulatory markers for metastasis are ongoing using multiplex platforms. The data for the same shall be presented.
Cancer Science Institute of Singapore, Singapore
Keynote: Novel autoantibody signatures in plasma exosomes as potential biomarkers for diagnostics and prognosis of non-small-cell lung cancer
Time : 10:15-11:00
Dr. Lingzhi Wang is a Senior Research Scientist at the Cancer Science Institute of Singapore and an Assistant Professor in the Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore (NUS). Dr. Wang obtained his M.Med. in Medicinal Chemistry from Chongqing Medical University in 1993. He continued his postgraduate studies in NUS and obtained his M.Sc. in Pharmacy and Ph.D. in Pharmacology in 2003 and 2008, respectively. Dr. Wang received the Medical Research Scientist Award from the National Medical Research Council (NMRC Singapore) in 2005, and the PhD Graduate Research Excellence Award from the American Association of Pharmaceutical Scientists (AAPS) at its Annual Meeting in 2008 (USA).
Lung cancer has one of the highest cancer-related mortality rates due to lack of efficient diagnostic approaches. Although the National Lung Screening Trial (NLST) has now shown that screening with low-dose CT (LDCT) scanning results in fewer deaths from lung cancer, high false positive rate can lead to anxiety, additional cost and morbidity associated with cancer treatment. Therefore, the discovery of novel biofluid derived non-invasive exosomal biomarkers for lung cancer is urgently needed to reduce over diagnosis due to LDCT screening. Exosomes are small (30-120 nm) vesicles containing nucleic acid and protein cargo. There is currently a lack of information regarding the association between exosomal proteome and the pathological condition of lung cancer. We conducted studies to evaluate the utility of plasma exosomal proteins as circulatory biomarkers for early detection of non-small-cell lung cancer (NSCLC) using the Sengenics immunome protein array technology, which affords the simultaneous screening of over 1600 functional proteins selected based on their involvement in the immune system. It leverages on its use of a biotin carboxyl carrier protein (BCCP) folding marker, which ensures correct folding of every protein immobilized on the array. Preliminary data from this study revealed multiple biomarker signatures in both early and late stage patient cohorts when compared to healthy controls. With the use of sequential bioinformatics analyses which implements a penetrance fold change and a recursive feature elimination algorithm, we have modeled the correlation and classification of identified biomarker signatures with significant ROC-AUCs in differentiating NSCLC patients of different stages and the prognostic potential of exosomal autoantibody signatures is under investigation.
Guangzhou Medical University, China
Keynote: CHD1L promotes lineage reversion of hepatocellular carcinoma through open chromatin for key developmental transcription factors
Time : 11:15-12:00
Ming Liu has received his PhD and Postdoctoral training at the Department of Clinical Oncology, the University of Hong Kong. He is currently a Professor at the School of Basic Medical Sciences, Guangzhou Medical University. He has been focusing on characterization of molecular pathogenesis of human hepatocellular carcinoma and has published more than 20 papers in reputed journals, such as Nature Medicine, Gastroenterology, Hepatology, etc.
High-grade tumors with poor differentiation usually show phenotypic resemblance with their developmental ancestral cells. Cancer cells that gain lineage precursor cell properties usually hijack developmental signaling pathways to promote tumor malignant progression. Oncogenic chromatin remodeling protein (CHD1L) might be important in this process. The association of CHD1L with HCC lineage reversion was systematically evaluated in cell line model, xenograft mouse model, genetically modified mouse model and HCC clinical samples. Chromatin immunoprecipitation followed by high-throughput deep sequencing was used to identify the potential molecular mechanisms. CHD1L was found closely associated with liver development and HCC tumor differentiation. Expression of CHD1L decreased during hepatocyte maturation and increased progressively from well-differentiated HCCs to poorly-differentiated HCCs. ChIP-sequencing found that CHD1L could bind to genes related to development. Bioinformatics-aided network analysis indicated that CHD1L might regulate networks associated with embryonic development. Overexpression of CHD1L conferred ancestral precursor-like properties of HCC cells both in vitro and in vivo. Inhibition of CHD1L reversed the malignant phenotype and sensitized HCC cells to Sorafenib treatment. Mechanism studies revealed that CHD1L could maintain open chromatin architecture at promoter regions of key developmental transcriptional factors. Significant correlation of CHD1L with hepatic lineage differentiation markers was also found in HCC patients. We proposed a novel mechanism that oncogenic chromatin remodeler CHD1L might drive HCC lineage reversion and maintain a chromatin status suitable for liver ancestral precursor cells. Further, inhibition of CHD1L might down grade poorly-differentiated HCCs, sensitize tumors to Sorafenib treatment and provide novel therapeutic strategies for this deadly disease.
Fudan University School of Pharmacy, China
Time : 12:00-12:45
Yonghua Yang is currently a Professor in the Department of Biochemistry & Pharmacology of Fudan University, China. He has obtained his BS in Organic Chemistry from Jilin University and continued his Postgraduate studies in Shanghai Institute of Materia Medica, CAS and obtained his PhD in Pharmacy and Pharmacology, respectively. He is working with trainees in his laboratory on the characterization and development of novel molecules significant in breast tumorigenesis. He has published as first author and senior author in recognized peer-reviewed journals, including Nature Cell Biology, EMBO J, PNAS, Cancer Research and Oncogene, etc.
Among autophagy related proteins, two proteins have attracted immense interest. One is the class III phosphoinositide 3-kinase (PI3K) vacuolar protein sorting 34 (VPS34), which forms numerous complexes with the core components p150 (Vps15), Beclin 1 and ATG14L to function in a variety of cellular and physiological events. Another one is the well-known autophagic adaptor protein, sequestosome-1 (SQSTM1, also known as p62 in humans). VPS34 and p62 play important roles separately in vesicle nucleation and autophagy progression. Both of them may also contribute to the development and progression of human cancers. However, the mechanism of VPS34 coordinating p62 in tumorigenesis remains elusive. We found that the expression of VPS34, documented for the phosphorylation of MEK and ERK is strongly correlated with tumorigenic activity of human breast cancer cells. VPS34 augments PKC-δ to p62 for its phosphorylation at Serine 349, leading to transcriptional expression of p62 through its affinity with Keap1 (Kelch-like ECH-associated protein-1) and positive feedback on the Nrf2-dependent transcription of oncogenes. Moreover, ablation of PKC-δ or p62 expression in MCF-7 cells abrogates VPS34-dependent tumor growth. We will present data to show that VPS34 stimulates tumor development mainly through PKC-δ phosphorylation of p62 and all the results suggest that VPS34-p62-PKC δ machinery may be a useful target for cancer therapy.