^10th World Congress on Biomarkers & Clinical Research October 18-20, 2017 Baltimore, Maryland, USA

Biography:

Yelizaveta (Lisa) Torosyan is an interdisciplinary MD/PhD Scientist with clinical background and extensive biomedical expertise including translational research with potential health care applications. She is currently working at the Center for Devices and Radiological Health, Food and Drug Administration (CDRH/FDA) and her research involves in silico synthesis of epidemiologic and genetic evidence for discovery of biomarkers indicative of device performance.  
 

Abstract:

Translational research involving pharmacoepidemiologic and pharmacogenetic applications is critically important for enabling access to safe and effective medical products. The ongoing efforts for predictive evaluation of real-world performance of medical devices at the Division of Epidemiology at the Center for Devices and Radiological Health include development of an in silico framework that is based on re-utilization of pre-existing epidemiologic and genetic data and that is aimed to identify candidate biomarkers indicative of device performance. The current presentation will share experience from a number of projects on the discovery of device-related biomarkers guided by epidemiologic evidence. As an example, a retrospective analysis of discharges from the Nationwide Inpatient Sample from Agency for Healthcare Research and Quality (NIS/AHRQ) will be presented as a preliminary step for the discovery of candidate SNPs using Personalized Medicine Research Project data on hip arthroplasty outcomes from Marshfield Clinic Research Institute (PMRP/MCRI). The presentation will also include use of causal analytics approaches (ingenuity pathway analysis) for exploring functional plausibility of the identified candidate SNPs indicative of periprosthetic osteolysis in the sex/race-stratified subpopulations with hip arthroplasty. As a result, the presentation will render new in silico approaches that reutilize pre-existing (genetic and epidemiologic) data and that thus can augment the evidentiary needs for development of cost/time-efficient precision medicine applications.

Biography:

Peter Schulz-Knappe is working as MD and Cell Biologist by training. He is a Board Member of biotech companies and serves as CSO since 1997. His scientific passion for the last 25 years has been in the discovery, validation and development of protein biomarkers from blood. His main research topics are: proteomics, peptidomics, biomarkers, autoantibodies, protein microarrays, IVD-development. He has published and co-authored over 100 peer reviewed papers. In addition, he is inventor of > 20 patents and patent families on peptides, biomarkers, and analytical procedures.

Abstract:

Autoantibodies (AAB) targeting self-antigens can be found in two clinically and immunologically opposing diseases, autoimmune diseases and cancer. While in autoimmune diseases, the immune system is hyperactivated against self-antigens, many tumors suppress the anti-tumor immune response. Therapeutic cancer vaccines are designed to generate an antigen-specific tumor response in cancer. To further augment the immune response, combination therapies of therapeutic vaccines with checkpoint inhibitors such as ipilimumab are currently tested in clinical studies. Ipilimumab is an antibody that blocks the immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). However, treatment with ipilimumab is associated with immune-related adverse events (irAEs). We investigated AAB profiles in cancer patients treated with therapeutic vaccines, ipilumumab, and combination therapy. Serum samples from cancer patients treated with therapeutic vaccines and/or ipiliumab therapy were tested for the presence of serum autoantibodies. Candidate antigens comprise immune-related and cancer signaling pathway proteins, autoimmune disease antigens and tumor-associated antigens. Samples were collected prior to treatment (T0 samples), at three and six month. In total, 87 AABs were found significantly different in patients with irAEs and those without irAEs. AABs associated with irAEs were also associated with overall survival. Analysis of pathways revealed that AABs predicting irAEs target cancer, cell cycle, cell adhesion and apoptosis pathways. We also found elevated levels of AABs in patients who do not experience irAEs. These AABs target proteins involved in inflammatory, adaptive and cellular immune response pathways or represent autoimmune disease antigens. Further studies in larger sample sets are needed to confirm these findings.

Biography:

Tao Lu is a tenure-track Assistant Professor and Principle Investigator at Department  of Pharmacology and Toxicology, and a member of Simon Cancer Center at Indiana University School of Medicine. She obtained her PhD degree from University of Toledo, School of Medicine, and finished her Post-doctoral training with the world renowned scientist Dr. George Stark at Cleveland Clinic, Ohio. Her research focuses on the discovery of novel regulators of NF-kB, particularly, on the epigenetic regulation of NF-kB and its role in cancer therapeutics. She won multiple awards at international scientific meetings. She has published near 50 papers with 2 being highlighted by F1000 Prime. She currently holds 2 provisional patents regarding NF-kB regulation and serves as the board member of 5 scientific journals.

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are notoriously challenging for treatment. Hyperactive nuclear factor κB (NF-κB) is a common culprit in both cancers. Previously, we discovered that protein arginine methyltransferase 5 (PRMT5) methylated and activated NF-κB. Here, we show that PRMT5 is highly expressed in PDAC and CRC. Overexpression of PRMT5 promoted cancer progression, while shRNA knockdown showed an opposite effect. Using an innovative AlphaLISA high throughput screen, we discovered a lead compound, PR5-LL-CM01, which exhibited robust tumor inhibition effects in both cancers. An in silico structure prediction suggests that PR5-LL-CM01 inhibits PRMT5 by binding with its active pocket. Importantly, PR5-LL-CM01 showed higher antitumor efficacy than the commercial PRMT5 inhibitor, EPZ015666, in both PDAC and CRC. This study clearly highlights the significant potential of PRMT5 as a therapeutic target in PDAC and CRC, and establishes PR5-LL-CM01 as a promising basis for new drug development in the future.

Biography:

Dr. Tomoaki Ito was received the M.D. in 2000 and the Ph.D.in medical science from Juntendo University, Tokyo, Japan. and postdoctoral studies from Stanford University School of Medicine. He is an assistant professor of Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, Shizuoka, Japan. His reseach interest includes Oncology and Cancer Biomarker.

Abstract:

Companion diagnostics provide information of the effective use of a drug or biological product to help physicians to decide appropriate treatment to the patients. Especially, in cancer field, new technologies such as next generation sequencing, are used to identify nucleotide mutation in the genome of biopsy tissue.

Cancer Panel analysis (Illumina) provides pre-designed, optimized oligonucleotide probes for sequencing mutational hotspots in > 35 kilobases (kb) of target genomic sequence. Forty-eight genes are targeted with 212 amplicons in a highly multiplexed, single-tube reaction.

We performed mutation analysis of the fresh Gastric cancertissues from 4 patients by Cancer Panel analysis using next generation sequencer (MiSeq). We found three hotspots mutations from two patients by comparison with normal tissues, and those mutations would be correlated with their clinical information.

Also, Cancer Panel analysis was successful for same tissues which were fixed by 5% of formalin within one day. Nucleic acid transition appeared in samples fixed for more than 3 days, but such error was not detected for samples fixed within a day. These results would be useful to establish guidelines of tissue fixation for protocols of DNA analysis.

Biography:

Victor Frenkel completed his PhD in 1999 at the Technion, Israel Institute of Technology. After a Post-doctoral Fellowship at the University of Maryland Biotechnology Istitute, he was a Staff Scientist at the National Institutes of Health Clinical Center, and Associate Professor of Biomedical Engineering at Catholic University in Washington, DC. He is currently working as an Associate Professor and Director of Translational Focused Ultrasound Research at the Department of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine. He has published more than 100 peer-reviewed original research articles, invited reviews, editorials, books and book chapters and conference abstracts.

Abstract:

One of the main impediments to succesful treatment of solid tumors is the inability to obtain sufficient and uniform delivery of therapeutic agents. This is due in part to unique characteristics of the tumor micro-environment, which include abnormalities in the tumor vasculature (such as leaky and tortuous vessels) and a dense and heterogenous extracellular matrix. The presence of these factors can result in deficiencies in transvascular and interstitial transport, respectively, which will ultimately affect the bioavailability and efficacy of administered therapeutics. We have shown how non-invasive and nondestructive, focused ultrasound (FUS) exposures provided in pulsed mode (pFUS) can enhance the delivery of therapeutic agents of various formulations in solid tumor models, including small molecules, antibodies, liposomes, nanoparticles and DNA. Studies were carried out using state of the art, image-guided FUS devices. Enhanced delivery was observed when employing both systemic and local injection, where therapeutic studies demonstrated significant improvements in tumor growth inhibition and survival. Mechanistic studies carried out to support these results showed increase in the effective pore size of the extracellular space, disruption of fibrillar collagen, increased hydraulic conductivity and lower interstitial fluid pressure of the tumor tissue. Preliminary studies were also carried out on the potential of the pFUS exposures on the metastatic process.

Biography:

Alexander M Buko received his PhD in 1980 from the University of Virginia under Professor Donald F Hunt. He went onto work at the Bureau of Biologics and Biophysics (Today called CBER) for four years then moved to Abbott Labs for 18 years as a distinguished research fellow. From 2002 to 2012, he was Sr. Director of Translational Medicine at Biogen Idec. Currently, he is the Vice President of Business and Product Development for HMT-America (Human Metabolome Technologies).

Abstract:

Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of low mood, independent of life experience. It is often accompanied by low self-esteem, loss of interest in normally enjoyable activities, low energy and pain without a clear cause. Major depressive disorder affected approximately 216 million people (3% of the world's population) in 2015 and is the leading cause of disability in the US for ages 15 to 44. MDD affects more than 15 million American adults, or about 6.7 percent of the US population aged 18 and older in a given year. The American Psychiatric Association added "major depressive disorder" to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. The diagnosis of major depressive disorder can be based on the person's reported experiences and a mental status examination. There is currently no laboratory or blood test for major depression. Two of the most common examinations are the CES-D and HAMD-17 scores. While the specificity of these scores can be close to 100%, the sensitivity can be as low as 40%, i.e., when the score diagnoses MDD, it can do so very well, however, more than half of the patients with MDD can be missed. Using metabolomics, HMT, in collaboration with Dr. Noriyuki Kawamura of the Gyokikai Medical Corporation we identified a plasma metabolite, phosphoethanolamine or PEA, that was consistently low in patients with clinically diagnosed MDD. PEA measured by it has over 90% sensitivity and specificity, but in conjunction with a clinical score can achieve close to 100% sensitivity and specificity for MDD. Low levels of PEA distinguish MDD from other forms of mental disorders such as schizophrenia, bipolar disorder or other anxieties. Early studies also suggest successful treatment where MSS, PEA levels are restored to normal. Multi-center large clinical studies in the US, Japan, Europe and in China are currently ongoing to validate the diagnostic utility of PEA for MDD patients. The talk will provide a walk-through the development process of PEA for MDD from early discovery to large scale clinical validation, from CE-MS discovery measurements to a recently released beta version clinical assay kit designed for large scale clinical measurements at independent laboratories.

Biography:

Melvin L DePamphilis received his PhD in Biochemistry from the University of Wisconsin, with Post-doctoral work in enzyme mechanisms at UW and tumor virus DNA replication at Stanford University Medical School. He is currently working as a Senior Research Scientist at the National Institutes of Health. Prior to that, he was a Professor in the Department of Biological Chemistry at Harvard Medical School, and then a Lab Chief at the Roche Institute of Molecular Biology. His professional career is focused on genome duplication in animal viruses, cells, and preimplantation embryos. He has published 147 research papers, 55 reviews, and 10 books.

Abstract:

Most cancers result from the accumulation of genetic mutations that occur during proliferation of the cells that give rise to and maintain tissues. Cancer driver mutations initiate carcinogenesis, but genome destabilizing mutations promote aneuploidy, which contributes to tumor heterogeneity, drug resistance, and treatment failure. Aneuploidy results from missegregation of chromatids during mitosis, which is promoted by aberrant genome duplication in the form of unscheduled endoreplication. At least 35 genes are essential to prevent endoreplication during mitosis and cytokinesis. Fourteen of these genes have been shown to prevent aneuploidy and tumors in mice. Thus, reducing expression of a gene essential to prevent endoreplication during cell proliferation facilitates the rise of cancer. Conversely, induction of aneuploidy can also prevent tumor formation. During mammalian development, pluripotent stem cells give rise to all cell lineages, but when they mislocate to ectopic sites, pluripotent stem cells act as cancer stem cells by producing germ cell tumors. Geminin is one of seven proteins that are essential to prevent DNA re-replication dependent apoptosis during cell proliferation. Although geminin is essential in cells derived from various human cancers, geminin is not essential in normal cells-with one exception. Geminin is essential to prevent DNA re-replication dependent apoptosis in pluripotent embryonic stem cells. Therefore Geminin is a potential chemotherapeutic target in the treatment of germ cell neoplasia, as well as any cancer whose origin depends on a pluripotent progenitor cell.

Biography:

Daniel Krainak obtained his PhD in Biomedical Engineering from Northwestern University and completed a Post-doctoral fellowship at CDRH investigating diffusion tensor imaging. He has been a reviewer in the division of Radiological Health since 2012 with an emphasis on magnetic resonance imaging technologies. He participated in the review of radiological devices, imaging biomarkers, and radiological imaging in therapeutic product clinical trials.

Abstract:

The Center for Devices and Radiological Health has responsibility for radiological device pre-market reviews and participates in biomarker qualification review teams for imaging biomarkers through the Medical Device Development Tools program (CDRH) and the Biomarker Qualification Program (CDER). CDRH’s perspective on the evidentiary approach to quantitative imaging devices and imaging biomarkers will be presented. A regulatory perspective on the interaction between claims and analytical validation expectations will be explored for radiological imaging devices. Combinations of technical performance assessments including combinations of physical phantoms, digital reference objects and in vivo imaging may be used to approach analytical validation of imaging devices. Differing evidentiary expectations will be presented with examples. Research within CDRH continues to refine and expand the available methods for assessing the performance of quantitative imaging biomarkers.

Biography:

Janio Szklaruk has completed his PhD in Physical Chemistry from the State University of New York at Stony Brook NY and his MD degree from the University of Pennsylvania School of Medicine. He completed his Residency in Diagnostic Radiology at Thomas Jefferson University Hospital in Philadelphia. He is the Director of Abdominal Imaging MR at MD Anderson Cancer Center. He is also the Co-Chief, ad interim, of the Abdominal Imaging Section in the Radiology Department at MD Anderson Cancer Center. He has published more than 60 papers and presented multiple talks at international conferences.           
 

Abstract:

Worldwide, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death with over 500,000 new cases occurring per year. Some of the risk factors associated with HCC include hepatitis B and C, cirrhosis, alcoholic liver disease and aflatoxin exposure. Multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) are commonly used in the diagnosis, staging, and surveillance of these patients. The purpose of this presentation is to demonstrate a step-wise approach to the radiological evaluation of patients suspected with HCC. The presentation will discuss the importance of the optimum imaging protocol and the common. The new LIRADS criteria for the diagnosis of HCC and the application of Gd-EOB-DTPA to the management of HCC will be presented. Relevant imaging information to provide appropriate staging for HCC will be presented. Following the treatment of HCC, the detection of recurrent disease also depends on imaging findings. The imaging patterns that distinguish post-treatment changes versus recurrent disease will be presented. The goals of this presentation are for the participants to (i) to learn the importance of optimum imaging protocols, (ii) to become familiar with the imaging features of HCC, (iii) to recognize the imaging patterns of recurrence following treatment.

Biography:

Satoshi Tokuda graduated from Juntendo University School of Medicine in Japan in 2012. From 2012-2014, he was a Junior Resident at Juntendo Shizuoka Hospital, Shizuoka, Japan; near the Mt Fuji. He has been a GI Surgeon at Juntendo Shizuoka Hospital from October, 2014, until now.

Abstract:

Introduction: The number of the patients of major depressive and bipolar disorders are increasing. Cancer and depression have a close relationship; about 16% of all cancer patients are diagnosed with it. In this study, we selected two genes as potential markers of the mood disorder and checked the amount of the gene expression in gastrointestinal cancer patients at several points.

Materials & Methods: Three patients who were diagnosed with gastrointestinal cancer were selected and we gathered blood samples. They had no medical examination of psychiatric disorder. The timings of sample collection were before operation, post-operative day 1 and almost seven days after the surgery. We gathered blood in PAXgene RNA tube. After extracting RNA, we measured the expression of two genes by Real-time PCR. All patients of this study signed written informed consent forms.

Results: We compared the gene expressions of before operation and post-operative day 1 and confirmed the reduction of the prevalence of mood disorder in three patients after surgery.

Discussion: Before an operation, the patients must have a lot of stress and after their surgery they experience relief from the stress. This study suggests that we can confirm the mood changes with numeric data. If we grasp the mood disorder in the early period of cancer patients, we can help the patients with early intervention of mental side. The optimal outcome is to increase the cases and use the markers in clinical application. Add to that, we will gather saliva specimens and measure the gene expressions as well. The reason is that we can get the patient’s saliva easily and utilize in various situations; e.g. disaster and little children.

Conclusion: The marker of the mood disorder is suggested by colon cancer patients.

Biography:

Martin Tobi completed his MB ChB (MD equivalent) from the University of Cape Town Medical School, South Africa, clinically trained in Jerusalem and Chicago, and Post-graduate Training at the NCI, NIH, Bethesda Maryland. He was the Chief of Gastroenterology at the Philadelphia VAMC and Faculty at the University of Pennsylvania Perelman School of Medicine. He currently is at the Saginaw VAMC working as Clinical Professor of Gastroenterology at CMUCOM and has an active laboratory at the Detroit VAMC. He has more than 80 articles in peer-reviewed publications and served on Editorial Boards, organized conferences and participated in study sections.

Abstract:

The p87 biomarker is recognized by an anti-adenoma murine monoclonal antibody (Mab), tailored for early detection of colorectal neoplasia in colonic effluent. The Mab functions for immuno-blotting, ELISA and immunohistochemistry (IHC). It recognizes an epitope on a 87 kDa 10% N-linked glycoprotein. It is constitutively expressed but at a low level in the human GIT. The cell of origin appears to be the paneth cell, a component of the innate immune system. Expression is increased in normal-appearing colonic mucosa comensurate to risk of colorectal cancer (CRC). It is found in tissues from all colon genetic syndromes and is increased in the stool of patients at increased risk for CRC. It is postulated to be the human analogue of the modifier of min (MOM). In the human, it increases with age but disproportionately increased in younger patients rectal mucosa mirroring the current epidemiologic trend. It can be differentially expressed in the serum of patients with cancer which suggests that it may have diagnostic utility for serum bank samples. It has prognostic capability in IHC for pancreatic cancer (adenocarcinoma and IPMN); gastric adenocarcinoma and CRC. Prospectively, it has been shown to have 52% sensitivity and 91% specificity in lung and 67% with 90% respectively in pancreatic cancer patients, diagnosing patients two years before the cancer was clinically diagnosed. Thus, the p87 biomarker therefore covers a gamut of most common cancers possibly giving most cancer victims a chance at early diagnosis in order to bring cancer therapy to bear at a earlier cancer stage.

Biography:

B Padmanabhan is working as a Professor and Head of the Department of Biophysics, NIMHANS, Bangalore, India. He is a Structural Biologist and has more than 22 years of work experience blended with industry and academic careers. He has worked in various international organizations including Mitsubishi Chemical Corporation, ERATO-JST, RIKEN in Japan, the University of Washington, Seattle, USA, Laurus Lab Pvt. Ltd., Hyderabad, India. His group is now focusing on structure-based drug discovery on the protein targets associated with neurological disorders including Parkinson’s disease (PD), ALS and glioma. He earned his PhD in Biophysics and Protein Crystallography from All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Abstract:

Epigenetics, through the modulation of genetic information, involve a fundamental life process, such as cell-proliferation, cell development and decision between cell survival and cell death. Alteration of epigenetic function, which causes abnormal cellular functions, can lead to the development of cancer, neurodegeneration, autoimmune/inflammatory diseases, metabolic diseases and viral infections. Hence, the epigenetic targets are of great importance to discover new drug molecules for various major diseases. One of the epigenetic ‘reader’ proteins, bromodomain containing proteins recognized acetylated-lysine histones (H3 and H4) and non-histones, such as the tumor suppressor, p53. The BET family nuclear proteins possess two tandem bromodomains (BD1 and BD2) and a conserved extra-terminal domain. The BRD2 protein, a BET family member, recognizes mono-acetylated and di-acetylated histones through N- and C-terminal bromodomains. The BRD2 protein are reported to possess potential role in the pathogenesis of cancer, defects in embryonic stem cell differentiation, seizures and neurodegenerative disorders. Drug discovery of small molecule inhibitors targeting BRD2/BRD4 are in the pipeline, and some of them are already in clinical trials for the treatment of cancer. We have recently discovered compounds, by structure-based drug design method, which significantly inhibit the second bromodomain, BD2 of BRD2. The crystal structures of the BRD2-BD2 inhibitor complexes were determined at atomic resolution by using the X-ray diffraction data collected on the beamline, BM14 at ESRF, France. The drug discovery process such as in-silico screening, co-crystal structure determination, binding study and cell-based assay of the BRD2-BD2 complex will be discussed.

Biography:

V Rohil has obtained his MBBS degree from University College of Medical Sciences, Delhi and MD in Biochemistry from V P Chest Institute and has joined the Department of Clinical Biochemistry, V P C I, University of Delhi in 2001 as Assistant Professor, after doing Senior Residency at Maulana Azad Medical College, New Delhi. He has more than 24 years of Professional experience in the medical profession out of which 16 years of experience he has got in Teaching, Diagnostics and Research in the field of Biochemistry, Clinical Biochemistry and Molecular Biology. He is Supervisor and In-charge of the Clinical Biochemistry Autoanalyzer Laboratory for patient care at the Viswanathan Chest Hospital at V P C I and he is actively involved in Research and Teaching and guiding Post-graduate MD and PhD Students. He was selected as Govt. of India Expert, Medical Faculty under Govt. of India assistance programme by Ministry of External Affairs on special deputation to work at the Dept. of Biochemistry at B P K I H S, Dharan, Nepal and taught Medical graduates and Post-graduates for three years in an integrated setup, thereby he has acquired skills in structured interactive session [SIS], laboratory exercises [LABEX], problem based learning [PBL], multi-system seminars [MSS] with integrated teaching along with newer improved assessment techniques like OSPE [Objective structured practical examination], MCQ, Item analysis, SAQ, MEQ etc.

Abstract:

Background: Cancer is a group of diseases involving abnormal cell growth, occasionally having metastasis. This underlying genetic disease is initiated either by mutation or epigenetics. We are targeting lung carcinoma, most common cause of cancer-related death in men and women. Our new drug discovery is targeted on Calreticulin Transacetylase (CRTAase). We intend to treat lung cancer in-vivo and in-vitro by inducing hyperacetylation and upregulating the expression of genes important in tumor suppression. The polyphenolic acetates in combination with HDAC inhibitors are known to promote hyperacetylation, leading to apoptosis in lung cancer cells.

Aim: To determine the anticancer activity of 7, 8-Diacetoxy-4-Methyl Coumarin (DAMC), Polyphenolic acetate targeting acetylated histone interaction.

Methodology: DAMC showed anticancer activity both in-vitro and in-vivo. The hyperacetylation activity of DAMC on CRTAase induced epigenetic modulations were observed in A549 cells, as well as mice with Ehrlich ascites tumor (EAT) cells. The in-vitro and in-vivo data was validated by the apoptosis. Additionally specific target based anticancer property of DAMC was evaluated using microarray and RTPCR prior and after demethylation.

Results: In A549 cells, highest transfection efficiency was obtained after 72 hrs. Significant increase (p<0.01) in expression of H3 (2.67±0.02) and H4 2.755±0.016) was observed in DAMC treated CRTAase gene transfected A549 cells as compared to non-transfected A549 cells treated with DAMC (2.14±0.023) and (2.161±0.011) respectively. High apoptotic index was observed in The EAT cells in-vivo as well as in A549 cells in-vitro. RNA having RIN (RNA Integrity) values between 8.5 and 9.8 on electropherogram were subjected to microarray and RTPCR. A549 cells treated with DAMC and Valproic acid (VA) were suggestive of synergistic upregulation of tumor suppressor genes viz. ING4, TCF21, MFSD2A, FHIT and metalloproteinase inhibitor 3 i.e.TIMP3 and downregulating the oncogene Skp2.

Conclusion: The in-vivo as well as in-vitro findings suggest that DAMC and VA can potentiate the apoptotic pathway via CRTAase and thus can be a very promising anticancer drug candidate. In further ongoing studies we are screening more drugs targeting similar/more molecular targets and extending correlation with clinical applications.

Biography:

Weiming Xia received his PhD degree from the University of Texas Medical School at Houston in 1994. He pursued his Post-doctoral training in Dennis Selkoe’s laboratory and became Assistant Professor at Harvard Medical School in 1999. Currently he is working as an Acting Associate Director of Research at GRECC, Bedford VA Hospital affiliated with Boston University School of Medicine. He has published over 110 original research articles and edited a book. His research focuses on the molecular mechanisms responsible for Alzheimer pathogenesis and biomarkers, and on exploration of therapeutic interventions.

Abstract:

Two pathological hallmarks of Alzheimer’s disease (AD) are Tau-containing neurofibrillary tangles and amyloid β protein (Aβ)-containing neuritic plaques. Due to the heterogeneity and multifactorial nature of AD, a single biomarker for diagnosis of AD has not been identified. In this study, we have collected peripheral blood mononuclear cells (PBMC) and plasma from AD patients and cognitive normal subjects. We have converted PBMC to induced pluripotent stem cell (iPSC) lines, and we have further differentiated iPSC into human 3D neurons. At autopsy, AD pathology was confirmed in brains of patients from whom we derived blood, iPSC and 3D neurons. Quantitation of Aβ and Tau by ELISA illustrated much higher levels of Aβ and phosphorylated Tau at residues Thr 181 and Thr 231 in brain tissue from superior and inferior frontal cortex area, compared to those from cerebellum region. Liquid chromatography/mass spectrometry was used to analyze plasma, iPSC, 3D neurons and post-mortem brain tissue labelled with isobaric mass tags for relative protein quantification. Our study revealed compartmental segregation as well as association of differentially expressed proteins between AD and control subjects. We found that the levels of Tau and neurofilament light and medium polypeptides were increased in 3D neurons derived from AD patients. Analysis of plasma samples also allows us to separate AD patients from healthy subjects. In conclusion, we present a unique platform to discover proteins linked to AD as candidate biomarkers.