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Conference Program
 
Metals in Medicine
Medicinal Inorganic Chemistry
June 27 - July 2, 2010
Proctor Academy
Andover, NH

Metals are essential to life and health, and given the success of Cisplatin as well as MRI contrast and radiopharmaceutical agents, a rapidly growing interest in developing inorganic medicinal alternatives has spawned the Metals in Medicine GRC. Medicinal Inorganic Chemistry is an emerging field combating diseases using an unconventional perspective, encompassing diagnostics and therapeutics, in healthcare. The low-molecular weights of carbon-based pharmaceutical frameworks, their historical connection to natural products, and their fundamental stability to hydrolysis, have allowed this industry to grow and mature to produce a refined drug pipeline. However, the need to conquer diseases continues, target complexity is increasing, and as bacterial resistance develops to many carbon-based drugs exploitation of less conventional strategies is needed. Cross disciplinary approaches allow several health related disciplines, including nutrition, to come together to develop novel treatment strategies. Several approaches to combat cancer will be presented, as well as studies and treatment approaches to other diseases, including diabetes, cardiac and pulmonary conditions, neurological disorders, stroke, renal diseases, aging, genetic defects and other illnesses. The Metals in Medicine Conference has grown into the meeting place of chemists, biochemists, biologists, pharmacologists, geneticists, toxicologists, nutritionists and clinical scientists with interest in the application of metals and other inorganic elements in health-related fields.

The atmosphere and participants at the Metals in Medicine conference have historically been both international and across academia and industry. The co-chairs and vice-chairs of this conference are elected to reflect the nationalities of the practitioners in the field and for the upcoming meeting the chairs are Debbie C. Crans (Colorado, US) and Jan Reedijk (the Netherlands) and the vice chairs are A. Dean Sherry (Texas, US) and Susan Berners-Price (Australia). To expand the participation of younger practitioners in this field the upcoming meeting will host pilot sessions developed based on abstracts from new participants in the area. The 2010 Metals in Medicine: Medicinal Inorganic Chemistry will therefore include a session dedicated to "Student/Post-doctoral", "Young Investigator and Newcomer to GRC", and "Young Industrial Participant" presentations. This session will allow us to showcase the promising young researchers in the Metals in Medicine area, as a fore-runner to the development of a Gordon Research Seminar (GRS) for Metals in Medicine.


Contributors

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pmDinner
7:30 pm - 7:45 pmWelcome / Introductory Comments by GRC Site Staff and Chairs
7:45 pm - 9:30 pmMetals in Disease - New Frontiers in Iron Homeostasis
The Metals in Medicine GRC covers a broad range of topics that have evolved to provide an alternative to the traditional carbon-based approach to drugs. The successes include Pt-based drugs as well as agents that are used as MRI imaging and radiopharmaceutical agents. Metals ions as vitamins are essential nutrients. They serve as key components in proteins, and countless places in metabolism. Indeed, iron homeostasis central to human well being, is maintained by many newly identified genes and impacts diseases afflicting millions of Americans with, e.g. hemochromatosis, Sickle Cell disease, Thalassemia, iron deficiency anemia and several disease of the central nervous system; iron levels are closely monitored by physicians. A recent example of the US FDA approval of the ultrasmall iron oxide nanoparticle ferumoxytol to treat iron deficiency in patients with chronic kidney disease. In this introductory session of the Metals in Medicine conference three presentations on processes associated with iron metabolism will be presented. First, current and future targets will be overviewed and presented. Second, a mechanistic presentation will illustrate the strategy of mechanistic studies paving the way for developments of devising a strategy for a cure. Finally, the third presentation involves the use of phenomenological data in nutrition to connect metal availability and disease state highlighting the many infections that eventually occur in this compromised human patient population.
Discussion Leaders: Debbie C. Crans (Colorado State) and Jan Reedijk (Leiden University)
7:45 pm - 8:15 pm Elizabeth Theil (CHORI, UC Berkeley)
"Iron in disease, a target for 21st century therapeutics"
8:15 pm - 8:25 pm Discussion
8:25 pm - 8:50 pm Andrew J. Ghio (Clinical Research, EPA, North Carolina)
"Iron and oxidative stress in normal and diseased tissue"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:25 pm Alvin Crumbliss (Duke University)
"Hijacking Fe: The mechanism of Fe transport from outside the outer membrane, across the periplasm, to the cytosol in a pathogenic bacterium"
9:25 pm - 9:30 pm Discussion
9:45 pm - Chair's Reception
MONDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmPlatinum Anticancer Agents
Clinical and pre-clinical studies on platinum-based antitumor agents will be presented. The chair will present new mechanistic results and developments in imaging and tracking of the intracellular fate of platinum drugs. In addition, the session chair will introduce the topic of new clinical trials, a theme to be further expanded on by invited speakers. Two industrial speakers will provide perspective on the latest clinical results of new agents and/or formulations in clinical trials as well as briefly give background on the processes of drug development including intellectual property, financing and regulatory (FDA approval) issues. Two academic speakers presentations will include description of (i) the chemistry, biology and clinical potential of a new class of drugs structurally distinct from that of the Cisplatin and (ii) the mechanistic and clinical implications of platinum drug cellular accumulation in Cisplatin-sensitive and resistant human tumor cells.
9:00 am - 9:10 amDiscussion Leader: Nicholas P. Farrell (Virginia Commonwealth University)
"Introduction"
9:10 am - 9:40 am Stephen B. Howell (Moores UCSD Cancer Center)
"Copper transporters regulate the cellular pharmacology of the platinum drugs"
9:40 am - 9:50 am Discussion
9:50 am - 10:20 am Ulrich Bierbach (Wake Forrest University, NC)
"Non-crosslinking platinum-acridine agents: a new strategy for tackling chemoresistant cancers"
10:20 am - 10:30 am Discussion
10:30 am - 11:00 am Coffee Break
11:00 am - 11:30 am Michael Gottesman (National Cancer Institute, NIH)
"Novel cellular mechanisms of resistance to platinum chemotherapeutics"
11:30 am - 11:40 am Discussion
11:40 am - 12:10 pm Evelyne Vuaridel (Debiopharm)
"Oxaliplatin Formulations"
12:10 pm - 12:30 pm Discussion and General Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmNew breaking topics I: Multidrug-Resistance, Alzheimers, and Epigenetic Mechanisms
Topics from areas in Multidrug resistance, Alzheimers and neurodegenerative illnesses, and Epigenic mechanisms of less common metals have been selected for presentation in this session.
Discussion Leader: Susan Doctrow (Boston University School of Medicine)
7:30 pm - 8:00 pm Charles E. McKenna (U Southern California)
"Translational potential on bisphosphonate nucleotide based drugs targeting beta polymerase"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Katherine J. Franz (Duke University)
"Design of Triggerable Chelating Agents as Potential Therapeutics against Alzheimer’s Disease"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Max Costa (Langone Medical Center, NYU)
"Epigenetic mechanisms of carcinogenesis probing the roles of Ni, As, and Cr"
9:20 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmResponsive Magnetic Resonance Imaging (MRI) Contrast Agents
This session introduced by Professor Angelique Louie covers the development of new metal ion based MRI contrast agents reporting on their environment through specific molecular recognition events. Such responsive agents would register changes in pH, temperature and even metabolite concentration and are presented by Eva Toth and by Janet Morrow. The development of MRI contrast agents that localize to a specific cell tissue type and may bind specifically to cell receptors or compounds on cell surfaces will be discussed by Silvio Aime and Yi Lu.
9:00 am - 9:10 amDiscussion Leader: Angelique Louie (University of California, Davis)
"Introduction"
9:10 am - 9:40 am Eva Toth (Centre de Biophysique Moleculaire, CNRS, Orleans, France)
"Enzymatically activated PARACEST agents"
9:40 am - 9:50 am Discussion
9:50 am - 10:20 am Yi Lu (U Illinois, Urbana)
"Functional DNA in Biosensing, Bioimaging and Targeted Drug Delivery"
10:20 am - 10:30 am Discussion
10:30 am - 11:00 am Coffee Break
11:00 am - 11:30 am Silvio Aime (I.F.M., Italy)
"Metal containing nanosized system of MR imaging"
11:30 am - 11:40 am Discussion
11:40 am - 12:10 pm Janet Morrow (SUNY, Buffalo)
"Lanthanide complexes as responsive agents for optical and MR imaging"
12:10 pm - 12:30 pm Discussion and General Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmNuclear Medicine, Radioimmunotheraphy and Applications
A session including aspects of nuclear medicine, radioimmunotheraphy and applications of some well-known and novel clinically used agents, including Technetium, and Flourine-18 under development. Industrial participation and approaches in academia for translational research to document recent developments on its way and in the clinics.
Discussion Leader: Alan Packard (Children’s Hospital, Harvard Medical School)
7:30 pm - 7:40 pmAlan Packard (Children’s Hospital, Harvard Medical School)
"Introducing current advances and challenges in nuclear medicine and radioimmunotheraphy"
7:40 pm - 8:10 pmJohn F. Valliant (McMaster U /Centre for Probe Development and Commercialization, Ontario)
"Development and Evaluation of New Approaches for the Preparation of Organometallic Molecular Imaging and Therapy Agents"
8:10 pm - 8:20 pm Discussion
8:20 pm - 8:50 pmSimon Robinson (Lantheus)
"Discovery and development of a 18F pyridazinone analog, BMS747158, for myocardial perfusion PET imaging"
8:50 pm - 8:55 pm Discussion
8:55 pm - 9:25 pmMartin Breichbiel (NIH)
"Therapy with α-Emitters or Moby Dick"
9:25 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmNew Investigator, Student, Postdoctoral and Industrial Session
Presentations were selected from abstracts submitted by attendees to the 2010 Gordon Conference by the chairs and presiders. This session will allow us to showcase the young and researchers that have not previously presented at a GRC. Potential presenters indicate at the time of submission of their application to the GRC for acceptance to the Gordon Conference whether they are interested in contributing to this session. There will be three categories for these presentations, a session for students and postdoctoral fellows, a session for new investigators (defined as having attended less than 5 Gordon Conferences in the past) and Industrial Contributors. To be eligible to be considered for this conference the potential presenter must either be a student, a post doctoral fellow, a young investigator or having attended less than five Gordon Conferences in the past.
Discussion Leaders: Trevor Hambley (University of Sydney), A. Dean Sherry (University of Texas, Dallas) and Brian Day (Aeolus Pharmaceuticals, Inc)
9:00 am - 10:45 amStudent and Postdoctoral Session
Discussion Leader: Trevor Hambley (University of Sydney)
9:00 am - 9:10 amNora J.C. Graf (MIT)
"Pt(IV) encapsulated PLGA-PEG nanoparticles for targeting integrins in tumors"
9:10 am - 9:15 amDiscussion
9:15 am - 9:25 amJody M. Jourden (U. California, San Diego)
"Hydrogen Peroxide Activated Matrix Metalloproteinase Inhibitors"
9:25 am - 9:30 amDiscussion
9:30 am - 9:40 amPeter W. Winter (Colorado State)
"Compartmentalization of insulin receptor by insulin and the insulin-like compound BMOV in live RBL-2H3 cells"
9:40 am - 9:45 amDiscussion
9:45 am - 9:55 amNatsuho Yamamoto (U. Sydney, Australia)
"Visualising the Uptake of Fluorescently Tagged Cobalt Chaperone Bioconjugates in Solid Tumour Models"
9:55 am - 10:00 amDiscussion
10:00 am - 10:30 amCoffee Break
10:30 am - 10:40 am Robert Radford (U. Cal. San Diego)
"Controlling Coordination Chemistry on Protein Surfaces"
10:40 am - 10:45 am Discussion
10:45 am - 12:00 pmYoung or New Investigators to GRCs
Discussion Leader: A. Dean Sherry (University of Texas, Dallas)
10:45 am - 10:55 amJennifer Dubois (Notre Dame)
"Iron Trafficking as an Antimicrobial Target -- a Strategy"
10:55 am - 11:00 amDiscussion
11:00 am - 11:10 amMi Hee Lim (University of Michigan)
"Development of Bifunctional Small Molecules Targeted To Metal-Aβ Species in Alzheimer's Disease"
11:10 am - 11:15 amDiscussion
11:15 am - 11:25 amSuzanne Lapi (Washington University)
"Development of Zr-89, a longer lived PET radionuclide for molecular imaging"
11:25 am - 11:30 amDiscussion
11:30 am - 11:40 amJennifer C. Lee (NIH)
"Insights into Copper Coordination and Copper-dioxygen Reactivity of alpha-Synuclein"
11:40 am - 11:45 amDiscussion
11:45 am - 11:55 amMaolin Guo (U. Massachusetts, Dartmouth)
"Novel profluorescent sensors for subcellular iron, copper and oxidative stress imaging in live neuronal cells"
11:55 am - 12:00 pmDiscussion
12:00 pm - 12:30 pmIndustrial Contributors
Discussion Leader: Brian Day (Aeolus Pharmaceuticals, Inc)
12:00 pm - 12:10 pmJohn L. McManus (Aeolus Pharmaceuticals, Inc.)
"AEOL 10150 - An SOD Mimetic with Potent Radioprotective Properties"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmMarc Robillard (Philips, NL)
"In Vivo Chemistry for Pretargeted Tumor Imaging in Live Mice"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
(Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair)
7:30 pm - 9:30 pmAdvances in The Design of Non-Pt Anticancer Agents
Clinical and pre-clinical studies on non-platinum-based antitumor agents will be presented as a follow up to the earlier session on Pt-agents. The chair will begin with an overview and new results and developments pointing to new promising drugs in the pipeline. Each of the speakers will cover different areas of non-platinum agents including, gold, and Ru. The targets, mechanism of action, pre-clinical and clinical implications will be described.
7:30 pm - 7:40 pmDiscussion Leader: Peter Sadler (University of Warwick, England)
"Introduction"
7:40 pm - 8:10 pm Sue Berners-Price (Griffith University, Brisbane Australia)
"Gold-based, mitochondria-targeted anticancer compounds"
8:10 pm - 8:15 pm Discussion
8:15 pm - 8:45 pm Michael J. Hannon (University of Birmingham, England)
"Metal helicates and medicinal possibilities"
8:45 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Chi-Ming Che (University of Hong Kong)
"Anti-cancer gold complexes"
9:20 pm - 9:30 pm Discussion and General Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmNew breaking topics II
Recent breakthroughs selected from areas in antimalarial drugs, Cu- and Fe-homeostasis from bacteria to patients and dermatology
Discussion Leader: Gail R. Willsky (The State University of New York, at Buffalo)
9:00 am - 9:30 am Bernard Meunier (Palumed)
"Heme as a key target for peroxide-containing antimalarial drugs"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am José Argüello (NSF/ Worcester Polytechnic Institute)
"Mechanisms of Copper homeostasis in eukaryotes and bacteria"
10:15 am - 10:30 am Discussion
10:30 am - 11:00 am Coffee Break
11:00 am - 11:30 am Peggy Carver (University of Michigan)
"Correlating plasma concentrations of iron and trace metal ions with Infection in patients undergoing long-term home total parenteral nutrition"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Lisa DeLouise (Dept. Dermatology, Rochester)
"Synthesis and characterization of quantum dots for application in studies of skin barrier function"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmTargeting, Detection and Combatting Disease
Drug efficacy is improved significantly upon targeting, but with the complexities associated with metabolism remain a goal that researchers have been combating for significant time. In this section some of the recent successes will be presented. First, new approaches to electronically detecting proteins will be presented. Second, the in vivo imaging and therapeutic efficacy of a tumor-targeted corrole directed at the human epidermal growth factor receptor will be described.
7:30 pm - 7:40 pmDiscussion Leader: Harry Gray (Caltech)
7:40 pm - 7:50 pm TBA (Poster presenter selected from participant posters on-site)
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:35 pm Thomas Meade (Northwestern)
"Electronically detecting proteins"
8:35 pm - 8:45 pm Discussion
8:45 pm - 9:00 pm Celine J. Marmion (Royal College of Surgeons in Ireland)
"Combating Cancer with Precious Metals: New Platinum Drug Candidates with Dual DNA Binding and Enzyme Inhibitory Activity"
9:00 pm - 9:10 pm Discussion
9:10 pm - 9:20 pmNicola J. Farrer (University of Warwick, UK)
"Photoactivatable platinum anticancer complexes"
9:20 pm - 9:30 pm Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDepart

Funding for this conference was made possible in part by 1 R13 GM093354-01 from the National Institute of General Medical Sciences. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

 
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