homecoming activities
The Physics and Cancer table at ASU’s Homecoming Parade October, 2011. Our Education and Outreach Coordinator, Pauline Davies, hosted the booth with student worker, Amanda Wilber, to educate the general public about the significant research being conducted within our Physical Sciences and Oncology center here at ASU.
Speaker: Ernst-Ludwig Florin, PhD.
Location: Goldwater 487
Date & Time: October 26th, 2011 4:00 p.m.
Title: Microtubules: A prototype for biological and manmade fiber bundles
Abstract: Microtubules are part of the cytoskeleton and are involved in a large number of fundamental cellular processes such as cell division or intracellular transport. Due to their essential role in cell division, they are among the most successful targets for anticancer therapy. Individual microtubules are 25 nm thin and up to 100 µm long tube-like biopolymers built from even smaller fibers called protofilmaments. The protofilament architecture leads to unusual mechanical properties, such as a length dependence of the persistence length, not found in any manmade material. In my presentation, I will describe recent experimental results and present a model that explains how the length dependence of the persistence length arises from the protofilament architecture and local interactions between adjacent filaments. Implications for the regulation ofmicrotubule stiffness in cells and possible evolutionary advantages of thiscontrol will be discussed. Finally, I will show that the model can be used to describe the mechanical response of a wide range of biopolymer bundles and may help for instance in the efficient design of new multifunctional materials based on carbon nanotubes.
To schedule a meeting with the speaker click here
If you have any questions, please contact Jill Kolp, email hidden; JavaScript is required, Series Coordinator
Speaker: Thai Tran, PhD. received his Ph.D. in molecular biology from Purdue University and was trained a as a postdoctoral fellow with Dr. Hallgeir Rui at the Kimmel Cancer Center, Thomas Jefferson University. Dr. Tran has background in molecular and cellular biology of cancer. His research focus is to investigate the molecular functions that govern cancer cell development and progression. Specifically, his research has centered on identifying molecular biomarkers in breast, pancreatic and esophagus cancers using the combined approaches of high throughput immunohistochemistry, molecular and cellular technologies. More recently, he has focused more on dissecting intratumoral heterogeneity at the single-cell level by analyzing gene expression profiles of individual cells freshly isolated from true human clinical samples. The primary goal of this study is to identify minute populations of cells that potentially play major roles in cancer progression and metastasis.
Location: Biodesign Auditorium
Web Cast: View Web Cast Video
Date & Time: October 20th, 2011 12:00 p.m.
Title: Discovery of Prolactin Signaling Pathway in Breast Cancer
Abstract: Breast cancer is the second leading cause of deaths among women. In the United States, an estimated 230,480 are diagnosed with breast cancer each year and, of these, 39,520 are expected to die from the disease. This devastating consequence is partly due our inability to detect and provide treatments while the tumor is localized to the breast. As a result, numerous efforts have been made to identify early breast cancer biomarkers. In my talk I will discuss the implications of a number of potential breast cancer biomarkers specifically focusing on the functions of prolactin and its downstream target, Stat5. Unraveling the details of this new mechanism illustrates the complexity of signaling pathways and the formidable challenge of designing chemical intervention.
Thank you and if you have questions please contact Amanda Wilber! And don’t forget, coffee will be served!
Amanda Wilber, Center for the Convergence of Physical Science and Cancer Biology
Arizona State University | P.O. Box 871504 | Tempe, AZ 85287
480.965.3860 | Fax: 480.965.6362
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Speaker: William M. Grady, MD, is a physician-scientist at the Fred Hutchinson Cancer Research Center and the University of Washington Medical School, Seattle, WA. He is the Roger C. Haggitt Professor of Medicine and section Chief of the Gastroenterology Division at the University of Washington Medical School. He is also a full member of the Clinical Research Division of the Fred Hutchinson Cancer Research Center. In addition to being the PI of a translational research program in GI oncology, he is a practicing gastroenterologist and is the Medical Director of the GI Cancer Prevention Program Clinic at the Seattle Cancer Care Alliance, which specializes in the care of individuals who have cancer family syndromes.
He is an independent NIH funded PI with experience in the study of the molecular and cell biology of gastrointestinal cancer. He is the PI of an R01 funded study to assess the role of deregulated signaling pathways in the formation of colon cancer and is a recognized expert in the study of transforming growth factor ß (TGF-ß) signaling in colon cancer. He is also the PI of an Early Detection Research Network (NCI) Project to identify novel early detection markers for colon neoplasms as well as a project PI of a P01 (RecQ helicases and Colon Cancer) to identify predictive molecular markers for colorectal cancers. He has received numerous awards including the Damon Runyon-Lilly Clinical Investigator Award, Presidential Early Career Award for Scientists and Engineers, Burroughs Wellcome Clinical Scientist Award in Translational Research, and is a member of the American Society of Clinical Investigation.
Location: Biodesign Auditorium
Web Cast: View Web Cast Video
William Grady gave a great lecture.
Since the audio to the first 2 slides didn’t record, we have retained the slides for the record but cut down their duration on screen. His audio now appears at 1’08.
A brief summery of the first 2 slides:
Colorectal cancer is one of the most common cancers that affects people around the world. In the United States, 155,000 people per year are diagnosed with colorectal cancer. Virtually all colon cancers develop from colon polyps, which are benign tumors called adenomas. These adenomas occur in 1/3 of people over the age of 40 and over time can become cancer. It takes roughly 10-15 years for an adenoma to become a cancer and only about 10% of adenomas will become cancer. The long duration of the adenoma-carcinoma sequence has allowed a study of gene mutations that occurduring this process. Some mutations, such as APC (adenomatous polyposis coli gene) occur early in the process and are thought to initiate the formation of the adenomas, whereas others are found in more advanced adenomas or cancers and are thought to drive the progression of the adenomas to cancer.
Grady began by explaining that colorectal cancer takes many years – up to 2 decades to manifest from the initial event of a mutated cell in the colon epithelium to invasive cancer. He went on to describe how several different mutations are responsible for the development of cancer.
Date & Time: October 10th, 2011 12:00 p.m.
Title: The Role of Epigenetic Alterations in Colon Cancer
Abstract: Colorectal cancer arises as the consequence of the accumulation of genetic alterations (e.g. gene mutations, gene amplification, etc.) and epigenetic alterations (e.g. aberrant DNA methylation, chromatin modifications, etc.) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic and epigenomic stability and resulting gene alterations appears to be a key molecular and pathogenic step that occurs early in the tumorigenesis process and permits the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes in a clone of cells to result in their ultimate transformation into cancer. It has also become clear that epigenetic alterations are common in many cancers and affect the formation and behavior of the tumors. With regards to DNA methylation, it is present normally throughout the majority of the genome and is maintained in relatively stable patterns that are established during development. In humans, approximately 70% of CpG dinucleotides carry this epigenetic modification. However, there are regions that are enriched for CpG dinucleotides, called CpG islands, that are present in the 5’ region of approximately 50-60% of genes and are normally maintained in an unmethylated state. In cancers, many of these CpG islands become aberrantly methylated, and this aberrant methylation can be accompanied by transcriptional repression. The significance of these epigenetic alterations in the pathogenesis of cancer has been a point of significant controversy. Nonetheless, there is sufficient data to demonstrate that the aberrant methylation of at least some of these genes, such as MLH1, can be pathogenetic in cancer. The aberrant methylation of MLH1 occurs in approximately 80% of sporadic MSI colorectal cancers, and the restoration of MLH1 expression and function by demethylating the MLH1 promoter in MSI colorectal cancer cell lines, strongly supports the idea that such aberrant methylation is a cause rather than a consequence of colorectal carcinogenesis. Furthermore, the epigenetic inactivation of MLH1 appears to proceed the onset of mutations in genes with coding region microsatellite repeats, such as TGFBR2, suggesting epigenetic events can predispose tumor cells to mutations that drive the tumorigenesis process. Indeed, aberrantly methylated genes HLTF SLC5A8, MGMT, MINT1, and MINT31 can be found in aberrant crypt foci, demonstrating that aberrant promoter methylation occurs early in the adenoma sequence, although it does not confirm that the aberrant methylation is a primary rather than a secondary event in the tumorigenesis process. The aberrant methylation of genes affects genes that are commonly targets of mutational inactivation in colon cancers and contributes to the deregulation of signaling pathways that are known to be important in these tumors. Finally, a subset of colorectal cancers that hypermethylate genes belong to a distinct subclass of colorectal cancers, termed the CpG island methylator phenotype (CIMP) has been identified and appear to have a worse prognosis. These aberrantly methylated genes have been shown to be early detection markers and prognostic markers for a variety of cancers and some methylated genes are already being used in clinically available assays in the United States. The potential for methylated genes to be used as risk stratification markers, early detection markers, and predictive markers is high, and it is anticipated that they will move into common clinical use in the future. Finally, therapies directed at these genetic and epigenetic alterations are under active development and hold the promise to improve the treatment of colorectal cancer.
Thank you and if you have questions please contact Amanda Wilber! And don’t forget, coffee will be served!
Amanda Wilber, Center for the Convergence of Physical Science and Cancer Biology
Arizona State University | P.O. Box 871504 | Tempe, AZ 85287
480.965.3860 | Fax: 480.965.6362
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Welcome Cynthia Buness!
Cynthia Buness has joined the Physical Sciences and Oncology Center as our new advocate, a role in which she will work with the local community to increase public awareness of our cancer research progress.
Buness, a science and law graduate of ASU, is well known in the Phoenix business and law communities. As an attorney for Motorola, she investigated claims that toxic chemicals were released by the company which polluted the Phoenix residential water supply. Buness worked with researchers worldwide to successfully defend the company from suits filed by different plaintiffs.
Buness also served on the Board of Directors for the Phoenix Zoo and founded the Conservation Fund Committee which raises money for projects to protect endangered species.
Buness has strong links to the ASU alumni community and is extremely excited to be working with the Physical Sciences and Oncology team.
“For me, it is very empowering to create public awareness of ongoing cancer research” Buness said.
“The Center has an amazing ability to bring leading scientists to the Valley and it is enriching to help and get involved.”
Buness is passionate about science and is glad to be on board. The PSOC is delighted to welcome her.
Melissa Campos
Speaker: Raoul Tibes, MD, PhD. is a physician-scientist who sees and treats patients with hematological malignancies as well as heads laboratory research efforts in leukemia research. Further, he is actively conducting early phase (Phase 1/2) clinical trials with novel molecular therapies/agents.
Location: Biodesign Auditorium
Web Cast: Unavailable
Date & Time: November 17th, 2011 12:00 p.m.
Title: Target Identification in Cancer Using RNA interference –
Accelerated Therapy Development in Leukemias
Abstract: The challenge in drug development has been the implementation of novel active treatment regimens in cancer. Despite a deeper understanding of molecular oncogenesis many therapeutic strategies have failed in the clinic, raising the questions if currently developed drugs are not active enough against the targets or the “true” molecular targets – the synthetic lethal vulnerabilities in cancer genomes – have not been discovered yet.
Many therapeutic strategies were developed based on findings from structural molecular abnormalities such as mutations, amplifications or expression changes. However, functional information of interfering with the biological system (that is a cancer cell) and measuring the outcome after inhibiting individual genes is difficult to discern from these “static” research approaches. In order to obtain functional information of target gene interference that could be exploited for design of rational combinations in leukemias, our laboratory adopted small interfering RNA (siRNA) methodologies to suspension-leukemic cells in vitro. The challenge up to now has been the insufficient transfection of these leukemia cells for high-throughput siRNA (HT-siRNA). After successful establishment of a HT-siRNA platform for leukemia suspension cells, we performed the first cytotoxic drug-siRNA kinome sensitizer screen in leukemias. In siRNA kinome screens with the most commonly used leukemia drug Cytarabine, we identified a putative master sensitizer kinase in combination with Cytarabine. The target kinase and combination was validated in secondary siRNA screens and with a pharmacological inhibitor respectively. Based on these results a clinical trial has been proposed testing the identified rational combination.
A similar approach has been performed with 5-Azacytidine, a commonly used drug in myelodysplastic syndrome (MDS, often a pre-leukemia state). Of close to 900 genes individually silenced in combination with 5-Azacytidine, inhibition of only one genes potently sensitized to 5-Azacytidine. In validation experiments we confirmed the validity of this genes as a sensitizer to 5-Azacytidine by secondary siRNA screens. As well as showed strong sensitization of combining a novel small molecule inhibitor in clinical development targeting the identified gene, in combination with 5-Azacytidine, both in vitro and ex vivo. Clinical trials concepts have been developed for this novel combination as well.
Through the RNAi functional genomics approach we have identified new targetable concepts in myeloid cells alone or with commonly used leukemia drugs that yielded novel testable hypothesis to rapidly translate into clinical development and new treatment strategies in leukemias. These examples demonstrate the tremendous power and utility of functional genomics utilizing siRNA to identify, rational targets and combinations in cancer treatment.
Thank you and if you have questions please contact Amanda Wilber! And don’t forget, coffee will be served!
Amanda Wilber, Center for the Convergence of Physical Science and Cancer Biology
Arizona State University | P.O. Box 871504 | Tempe, AZ 85287
480.965.3860 | Fax: 480.965.6362
email hidden; JavaScript is required