2015 Archived Content


The ubiquitin proteasome system (UPS) is an essential and highly regulated mechanism operating to tightly control intracellular protein degradation and turnover. Recently, researchers have found new ways to chemically modulate this cellular machinery, thereby altering protein homeostasis as a therapeutic strategy and providing new avenues for pharmacological development. In particular, specific components of the UPS, such as E3 ligases, deubiquitinases (DUBs) and ubiquitin-like protein (Ubl) activating enzymes are quickly emerging as promising targets as they provide specificity for chemical matter, with the ability to alter cellular processes within a wide range of disease indications. As new biology and tools emerge, novel UPS inhibitors are rapidly being developed and optimized for clinical studies -  collectively setting the foundation for a new generation of therapeutics.

Cambridge Healthtech Institute’s third annual Targeting the Ubiquitin Proteasome System will once again gather an interdisciplinary collection of leaders working to advance the rapidly expanding field of UPS drug discovery.

Final Agenda

Day 1 | Day 2Targeting The Unfolded Protein Response | Download Brochure

Tuesday, September 22

7:00 am Registration and Morning Coffee


8:00 Chairperson’s Opening Remarks

Xavier Jacq, Ph.D., Head of Biology, MISSION Therapeutics

8:10 FEATURED PRESENTATION: Diverse Mechanisms of Allosteric Activation in DUB Enzymes

Titia Sixma, Ph.D., Professor, Head of Division and Group Leader, Biochemistry, Netherlands Cancer Institute

Deubiquitinating enzymes are frequently kept under tight control and only activated at the right time and the right site. For a number of different DUBs allosteric mechanisms of regulation have been identified and these present interesting new opportunities for targeting. Even in comparative similar USPs or UCHs, different regulatory mechanisms have been observed. We study the enzymology of different DUBs structurally and biophysically. Here we discuss how USP4 and USP7 have different regulatory mechanisms with a common catalytic switch. We also discuss how UCH-L5 can be switched on and off by structurally related regulators in the context of the proteasome and the INO80 chromatin remodeller respectively.

8:40 Parkin and USP30 Signaling in Parkinson’s Disease

Christian Cunningham, Ph.D., Scientist, Early Discovery Biochemistry Department, Genentech

Here we investigate the mechanism by which Parkin and USP30, a mitochondria-localized deubiquitinase, regulate mitophagy. We find that mitochondrial damage stimulates Parkin to assemble Lys6, Lys11, and Lys63 chains on mitochondria, and that USP30 is an ubiquitin-specific deubiquitinase with a strong preference for cleaving Lys6 and Lys11-linked multimers. Using mass spectrometry, we show that recombinant USP30 preferentially removes these linkage types from intact ubiquitinated mitochondria and counteracts Parkin-mediated ubiquitin chain formation in cells. These results, combined with a series of chimera and localization studies, afford insights into the mechanism by which a balance of ubiquitination and deubiquitination regulates mitochondrial homeostasis. Our model predicts that Parkin mutants with reduced activity could be therapeutically compensated by inhibition of USP30 and that inhibition of DUBs may have broader utility in counteracting autophagy impairment beyond mitophagy.

9:10 Investigating Deubiquitination with Small Molecule and Ubiquitin-Based Probes

Zhihao Zhuang, Ph.D., Associate Professor, Department of Chemistry & Biochemistry, University of Delaware

Deubiquitinases (DUBs) play essential roles in a number of cellular processes and are implicated in many human diseases. In cells individual DUBs are linked to specific cellular pathways, making them attractive targets for small molecule modulation. DUBs are also known to possess different types of ubiquitin chain linkage specificities. Understanding the DUB chain linkage specificity requires new probes to be developed. The probes can also be used to understand the different modes of ubiquitin chain binding and cleavage by DUBs.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing


10:25 Selective De-Ubiquitylase Inhibitors for Cancer Immunotherapy

Tauseef R. Butt, Ph.D., President and CEO, Progenra, Inc.

Although the ubiquitin pathway remains a highly attractive drug target, no one has taken a de-ubiquitylase (DUB) drug to the clinic. This failure is attributed to poor screening technologies, the inability to develop selective compounds, and even to the notion that DUBs are “un-druggable”. Progenra has discovered selective USP7 inhibitors that demonstrate efficacy in a number of p53-positive and p53-negative animal tumor models. An interesting finding is that USP7 inhibitors block cancer growth in immunocompetent mice; these molecules impair Treg functions, thereby promoting T effector-mediated anti-tumor activity. USP7 is overexpressed in multiple myeloma, neuroblastoma, prostate, bladder, colon, liver and lung cancers, and its expression is inversely correlated with survival in multiple myeloma, and correlated with tumor grade in prostate cancer. In addition to their immune mediated antitumor role, the USP7 inhibitors have also demonstrated direct anti-tumor activity in several models. Molecular mechanisms of these dual-acting USP7 inhibitors will be discussed. These unexpected findings indicate that USP7 is an important node in cancer and a compelling target for tumor therapy. USP7 inhibitors could be combined with other cancer immunotherapies to achieve durable clinical responses.

10:55 Proteasome-Associated DUBs: Molecular Targets for Cancer Treatment

Martina Bazzaro, Ph.D., Assistant Professor, Masonic Cancer Center, University of Minnesota

Recent work from our laboratory has shown that pharmacological inhibition of the proteasome-associated USP14 and UCHL5 has preclinical efficacy in preclinical models without toxicity in the host. Furthermore, we have shown that primary ovarian cancer cells derived from patients with recurrent ovarian cancer are particularly sensitive to USP14/UCHL5 inhibition. Importantly, we have shown that exposure of cancer cells to sublethal concentration of USP14/UCHL5 inhibitors causes ER stress responses and activation of autophagy. This suggests that inhibition of this class of enzymes results with an attempt of cancer cells to activate alternative and compensatory pathways to protein degradation. This concept is supported by our most recent data showing that both pharmacological and genetic inhibition of autophagy, potentiate the cell killing effects of USP14/UCHL5 inhibitors in cancer cell lines. Thus, we believe in the significance of taking advantage of the new weakness of chemoresistant ovarian cancer cells (i.e higher dependency upon USP14/UCHL5 activity) AND the cellular responses to USP14/UCHL5 inhibition to design a rational combinatorial approach with autophagy inhibitor to treat recurrent ovarian cancer. Importantly the combination approach proposed here has potential to achieve significant anti-cancer activity using much lower doses of the individual compounds thus limiting off-target toxicity and ultimately side effects on patients. This aspect being particular important for the cancer patient population, which responds well to standard chemotherapy but is often too debilitated to undergo a much needed second round of effective treatment.

11:25 Characterization of the Biochemical and Biological Activities of Proteasome Deubiquitinase Inhibitors

Padraig D’Arcy, Ph.D., Associate Professor, Cancer Pharmacology, Department of Oncology and Pathology, Karolinska Institute

The proteasome has emerged as an important target for anti-cancer drug development. We previously identified the small molecule b-AP15 as a novel class of proteasome inhibitor that functions by abrogating the deubiquitinase (DUB) activity of the proteasome. An optimized lead of this compound, named VLX1570, has subsequently been developed. b-AP15/VLX1570 are reversible and competitive inhibitors of the USP14/UCHL5 proteasome deubiquitinases (DUBs). b-AP15/VLX1570 are electrophilic compounds, but nevertheless show specificity to proteasome DUBs. Exposure to these drugs results in blocking of proteasome function as evidenced by the accumulation of polyubiquitinated proteins at the proteasome. Treatment with b-AP15/VLX1570 generates a robust proteotoxic stress response characterized by up-regulation of chaperone expression, ER and oxidative stress followed by apoptosis and cell death. VLX1570 shows in vivo activity in models of multiple myeloma and has recently been improved for clinical studies.

PerkinElmer NEW 200911:55 Next Generation Deubiquitinase Assays using Novel Tetraubiquitin Substrates and AlphaLISA Technology

Jeanine M. Hinterneder, Ph.D., Applications Scientist, Global Discovery Applications Group, PerkinElmer, Inc.

In order to make more biologically relevant deubiquitinase assays, we combine AlphaLISA technology with Tandem Ubiquitin Binding Entities to screen for DUB cleavage of Novel Tetraubiquitin substrates of at least three specific linkages. Here, we present data illustrating the utility of these assays as a tool in drug discovery programs.

Ubiquigent12:10 pm Enabling and Supporting Ubiquitin System Drug Discovery

Jason Brown, Ph.D., Scientific Director, Ubiquigent Limited

Targets across the ubiquitin system offer a significant opportunity for the development of novel therapeutics. Ubiquigent’s mission is to facilitate and support such drug discovery programmes. This is enabled through our provision of a wide array of tools and services (including our industry leading DUB inhibitor profiling service) whose applications will be reviewed in this presentation along with our future plans.

12:25 Session Break

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing


1:50 Chairperson’s Remarks

Gerald Gavory, Ph.D., Head, Biology, Almac Discovery

2:00 Discovery of Highly Selective DUB Inhibitors With in vivo Preclinical Anti-Tumour Activity

Xavier Jacq, Ph.D., Head, Biology, MISSION Therapeutics

Using a combination of synthetic lethality screens and isogenic cell line models, depletion of a number of deubiquitylating enzymes (DUB) was shown to selectively kill a range of different tumour types, including platinum-resistant ovarian cancers, DNA damage response pathway deficient tumours (e.g. ATM, ATR, BRCA2) and haematological tumours such as multiple myeloma. Illustrating our DUB target identification platform, USP11, was identified as an essential enzyme for the proliferation of platinum-resistant cells but not platinum-sensitive tumour cells in an isogenic model derived from patient tumours before and after development of resistance. Target validation of specific DUBs, like USP11, in genetic backgrounds corresponding to deficiencies found only in tumour cells associated with specific cancers, supported our rationale to develop DUB inhibitors for the treatment of cancers with unmet medical need. A broad drug discovery platform combining unique biochemical, cellular, biophysical and structural assays was designed to identify and optimise potent and selective DUB inhibitors. Early selective DUB hits have been successful in recapitulating synthetic lethality genetic evidences in matched isogenic backgrounds. Lead optimisation of early hits has recently been translated into compounds with adequate properties for in vivo proof-of-concept studies. The challenges and advances in demonstrating in vivo DUB target engagement will be discussed.

2:30 Development of Novel and Selective Inhibitors of USP7 with Cellular Activity

Gerald Gavory, Ph.D., Head, Biology, Almac Discovery

Ubiquitin specific proteases (USPs) are cysteine proteases that catalyse the de-ubiquitination of numerous protein substrates including tumor suppressors and oncogenes, hence regulating their levels and/or functions. USPs therefore represent a fast growing and attractive target class for pharmacological intervention. USP7 in particular has attracted considerable attention for its implications in multiple key oncogenic pathways including most notably MDM2/p53, PTEN and DNA damage. As part of a focussed effort towards targeting USPs, fragment screening was performed against a panel of family members, including USP7. Hits were identified by surface plasmon resonance and validated using orthogonal biophysical techniques (NMR, thermophoresis). Subsequent hit expansion identified molecules for which high-resolution co-crystal structures have been solved providing unique opportunities for structure-based design. Medicinal chemistry optimisation has yielded a series of novel, reversible and potent USP7 inhibitors (e.g. IC50 < 10 nM) with excellent selectivity profiles against deubiquitinating (DUBs) and other non-related enzymes. These inhibitors are cell-permeable and also exhibit potent target engagement in cells (e.g. IC50 < 30 nM) In line with the mechanism of action, further cellular profiling has demonstrated effects on p53, p21 and MDM2 levels in a concentration-dependant manner. From a translational viewpoint, initial studies aimed at identifying cell lines sensitive to these inhibitors will also be discussed. In summary, we report the discovery and detailed biochemical and cellular profiling of novel, potent and selective inhibitors of USP7. These molecules have drug-like properties and may provide opportunities for the development of new anticancer therapeutics.

Avacta Life Sciences3:00 Affimers: Novel Engineered Protein Tools to Explore the Protein Ubiquitylation System

Paul Ko Ferrigno, Ph.D., CSO, Avacta Life Sciences

Affimers are small, robust engineered proteins. Like antibodies, they are able to bind to target molecules (small molecules, lipids, peptides, proteins etc) with high affinities and exquisite specificities. Using in vitro phage display screening strategies that ensure that binders are fit-for-purpose, we have identified Affimers specific for various ubiquitin linkages (K6, K33, K48) as well as for human SUMO1 and, uniquely, SUMO2 and are beginning to explore DUBs such as OTUD5. Our goals are now to create a comprehensive toolbox of reagents that can be used to explore the biology of the protein ubiquitylation system and its role in disease.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Winner Announced


4:10 New Strategies for the Identification of Chemical Inhibitors of E2 Enzymes: The Problem with Ubc9

John ‘Jay’ Schneekloth Jr., Ph.D., Investigator, Chemical Biology Laboratory; Head, Chemical Genetics Section, Center for Cancer Research, National Cancer Institute, NIH

In this talk, I will discuss my group’s recent efforts to target E2 ubiquitin and ubiquitin-like conjugating enzymes, with a focus on Ubc9, the SUMO E2 enzyme. In addition to discussing the challenges associated with drugging E2 enzymes, I will describe the development and application of a high throughput electrophoretic mobility shift assay to screen for natural product inhibitors of sumoylation. Additionally, I will describe my group’s use of fragment-based inhibitor discovery techniques to develop inhibitors of Ubc9.

4:40 Novel Fluorescent Probes UbiFlu to Measure the Activity of E3 Ubiquitin Ligases.

Alexander Statsyuk, Ph.D., Assistant Professor, Department of Chemistry, Northwestern University

In this talk we will present our work toward the rational and systematic approaches to develop small molecule inhibitors of ubiquitin ligases (>600 known). Our initial efforts focus on the most well studied and simplest E3 ubiquitin ligases comprising HECT and RBR E3s. These are single subunit ligases that harbor the catalytic cysteine and form the obligatory HECT E3/RBR E3~Ub thioesters prior to ligation of the ubiquitin onto the lysines of protein substrates. Representative members of HECT and RBR E3s include ubiquitin ligases Nedd4-1, Nedd4-2, ITCH, Parkin, and E6-AP. These enzymes are involved in cancers, viral budding, neurodegenerative diseases, and autoimmune disorders, and therefore represent a viable drug targets to pursue. In spite of their promise as drug targets, HTS screen to identify inhibitors of HECT and RBR E3s are complicated and require 8 reagents in total including E1 and E2 enzymes. Such complexity makes HTS screening assays operationally complex and expensive. Furthermore, false positive results are produced due to the off-target inhibition of E1 and E2 enzymes. To overcome these challenges we have discovered a paradoxical phenomenon in which protein ubiqutination can be achieved in the absence of ATP, E1, and E2 enzymes. Based on this discovery we invented a novel class of probes UbiFlu that allow us to design novel assays to screen for inhibitors and activators of E3s. In contrast to commercially available assays that require 8 reagents, our assay requires only 2 reagents. We will discuss our basic research studies aimed at understanding the reaction mechanism of UbiFlu probes with HECT and RBR E3s, since these studies are crucial to understand better how to use UbiFlu in HTS assays, and how to interpret the data.

5:10 Interactive Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Discussing DUBs: Biological Rationale, Achieving Selectivity, and Transition into the Clinic

Moderator: Xavier Jacq, Ph.D., Head of Biology, MISSION Therapeutics

  • Many DUBs have functional implications in biological processes such as the DNA Damage Response Pathway (USP7, USP1, USP2, USP10, USP 47, USP16, USP 22 and USP 29), endosomal trafficking or cell signaling. What are other pathways and associated DUBs that are emerging?
  • DUBs as drug targets: Given the highly conserved catalytic cleft, how do you achieve selectivity while targeting DUB enzymes?
  • Why would you not achieve selectivity by targeting DUB catalytic sites?
  • What possible safety issues would you expect by targeting DUBs?
  • What are patient selection strategies for DUB inhibitors and how robust is the rationale?
  • How much redundancy/resistance do you expect with DUB inhibitors?
  • How to combine DUB inhibitors with standard or care treatments? Combination therapies?

Challenges and Opportunities for Ubiquitin Ligase Drug Discovery

Alexander Statsyuk, Ph.D., Assistant Professor, Department of Chemistry, Northwestern University

  • How to select E3 enzymes for drug discovery purposes? For example in the kinase field, tyrosine kinase Src is important, yet selective Src-kinase inhibitors have never made it to the clinic. How do we select the right E3s as drug targets? Can we learn the lessons from the kinase field? How are kinases selected, and how do we not select Src-type E3s, but rather Abl/RAF/EGFR type E3s as drug targets?
  • E3 enzymes can perform two enzymatic functions: substrate monoubiquitination (polyubiquitin chain initiation) and substrate polyubiquitination (polyubiquitin chain elongation or processivity). It is becoming evident that protein monoubiquitination regulates protein localization, while polyubiquitination leads to protein degradation. Question: Will the inhibition of polyubiquitin chain elongation but not initiation be therapeutically useful? In other words will the inhibition of substrate polyubiquitination but not monoubiquitination be therapeutically useful? In what cases?
  • Are other components of UPS system such as E2 enzymes neglected as therapeutic targets? E2 enzymes are viewed as simple messengers that shuttle between E1 and E3 enzymes. Inhibition of E2 enzymes should inhibit the activity of all respective downstream E3s. Are E2 enzymes good drug targets? Can E2 enzymes cause human diseases?
  • Are E1 enzymes viable drug targets?


Harnessing the Ubiquitin-Proteasome System for Post Translational Induced Protein Degradation 

Moderator: John ‘Jay’ Schneekloth Jr., Ph.D., Investigator, Chemical Biology Laboratory; Head, Chemical Genetics Section, Center for Cancer Research, National Cancer Institute, NIH

  • Discussion topics to be announced

6:10 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day

Day 1 | Day 2 | Targeting The Unfolded Protein Response | Download Brochure

Wednesday, September 23

7:30 am Registration and Morning Coffee


8:00 Chairperson’s Remarks

John ‘Jay’ Schneekloth Jr., Ph.D., Investigator, Chemical Biology Laboratory; Head, Chemical Genetics Section, Center for Cancer Research, National Cancer Institute, NIH

8:10 Strategies for Enhancing Proteasome Inhibitor Efficacy

Jonathan Blank, Ph.D., Senior Scientist, Biochemistry, Takeda Oncology

The 20S proteasome core particle contains two copies of three catalytic subunits, each with differing proteolytic specificity (β1: caspase-like; β2: trypsin-like and β5: chymotrypsin-like). Bortezomib (VELCADE®) and ixazomib (Takeda’s oral proteasome inhibitor, currently in clinical trials) primarily inhibit β5 (~5 nM IC50), with 10-fold lesser potency against β1, while β2 inhibition is much weaker (>1 µM IC50). We therefore investigated whether targeting of β2 could represent an alternate approach to inhibit the proteasome and have an anti-cancer effect. We describe a novel class of non-covalent dipeptide inhibitors possessing nano-molar potency for the β2 site in vitro with high selectivity over the β1 and β5 sites that can potentiate the effect of β5 inhibition with bortezomib or ixazomib, suggesting a strategy for combining proteasome inhibitors in disease settings with limited sensitivity to these agents.

8:40 In situ Generated Activity-Based Probes for Ub/Ubl E1-E2-E3 Enzymes: Structure, Activity and Biological Sensing

Farid El Oualid, Ph.D., CSO & COO, R&D, UbiQ

I will present the design and characterization of the first full-length Ub/Ubl-based activity-based probes (ABPs) for the E1-E2-E3 cascade. The ABPs are processed as native Ub/Ubl and at the same time allow covalent trapping of the active site cysteine of E1-E2-E3 enzymes (HECT and RBR type). I will discuss how these new ABPs can be used for activity-based protein profiling (of cell lysates and live cells) and structural biology experiments (of HECT, RBR and RING type ligases).

9:10 Inhibition of E2/E3 Protein-Protein Interaction as Novel Strategy to Interfere with E3 Ligase Activity

Kamyar Hadian, Ph.D., Head, Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, German Research Center for Environmental Health (GmbH)

This lecture will give insights into the discoveries of a novel E2/E3 protein-protein interaction inhibitor that we were able to validate and characterize in a variety of biochemical as well as cell-based assays. More importantly, we can show that this compound is also effective in an in vivo mouse model. Hence, we provide evidence that disrupting E2/E3 interactions may be a valid strategy to target E3 ligase activity.

9:40 Coffee Break in the Exhibit Hall with Poster Viewing


10:25 FEATURED PRESENTATION: Targeting Protein-Protein Interactions and Surfaces of Cullin RING E3 Ubiquitin Ligases (CRLs) with Chemical Probes

Alessio Ciulli, Ph.D., Associate Professor & Principal Investigator, Chemical & Structural Biology, College of Life Sciences, University of Dundee

This talk will describe current progress from the lab with developing and characterising small molecules targeting Cullin RING E3 Ubiquitin Ligases (CRLs). CRL-targeting chemical tools can be used alone as E3 ligase inhibitors or modulators of the biological pathway in which the specific CRL is involved. In addition, CRL-targeting ligands can be suitably tethered with a ligand for a given protein of interest, yielding bifunctional proteolysis targeting chimeras (PROTACs) to hijack the ubiquitin proteasome system and induce the intracellular degradation of the target protein.

10:55 Targeting Ubiquitination Activity of RING Domain in Cancer with Small Molecules

Tomasz Cierpicki, Ph.D., Assistant Professor, Pathology, University of Michigan

Targeting the Ring E3 ligases with small molecules is a very challenging task due to the lack of well-defined substrate binding pockets and a complex biochemical assays required for enzymatic activity studies. To identify small molecule inhibitors of Ring1B-Bmi1 we performed fragment-based screening using NMR spectroscopy. We identified a class of compounds that directly bind to Ring1B-Bmi1 and block its ubiquitination activity on H2A. We then performed extensive medicinal chemistry optimization of these compounds and substantially improved binding affinity, resulting in compounds that bind to Ring1B-Bmi1 with low micromolar affinities. Using structural studies we determined that these compounds induce significant conformational changes of the protein upon binding. We have performed characterization of in vitro and cellular activities of our best inhibitors and found that these compounds specifically inhibit Ring1B-Bmi1 ubiquitin ligase activity at low micromolar concentrations without inhibiting other RING E3 ligases that ubiquitinate histone H2A. Treatment of several cancer cell lines with Ring1B-Bmi1 inhibitors revealed robust downregulation of H2A K119 ubiquitination and increase in p16 expression. Furthermore, treatment with Ring1B-Bmi1 inhibitors impairs self-renewal of leukemia initiating cells. Our approach to target Ring1B-Bmi1 validates that RING ligases are ‘druggable’ targets.

11:25 Enjoy Lunch on Your Own

12:55 pm Plenary Keynote Program:

Comprehensive Kinase and Epigenetic Compound Profiling

Kelvin LamKelvin Lam, Ph.D., Director, Strategic Partnerships, Reaction Biology Corporation

Kinase inhibitors can be used as chemical probes to understand signal transduction pathways. Since the majority of kinase probes inhibit multiple kinases, understanding the off-target effects will allow scientists to design better poly-pharmacologic compounds to meet specific therapeutic needs. Profiling a compound against the entire kinase gene family will allow us to understand the compound’s full enzymatic activities. Unexpected activities could lead to different chemical design and possibly novel therapeutic opportunities. Reaction Biology offers large-scale in vitro kinase and epigenetic profiling services for (1) compound prioritizing and (2) elucidating novel activities for kinase and epigenetic inhibitors.

iPS Cell Technology, Gene Editing and Disease Research

Rudolf JaenischRudolf Jaenisch, M.D., Founding Member, Whitehead Institute for Biomedical Research; Professor, Department of Biology, Massachusetts Institute of Technology

The development of the iPS cell technology has revolutionized our ability to study human diseases in defined in vitro cell culture systems. A major problem of using iPS cells for this “disease in the dish” approach is the choice of control cells because the unpredictable variability between different iPS / ES cells to differentiate into a given lineage. Recently developed efficient gene editing methods such as the CRISPR/Cas system allow the creation of genetically defined models of monogenic as well as polygenic human disorders.

The Evolutionary Dynamics and Treatment of Cancer

Martin NowakMartin Nowak, Ph.D., M.Sc., Professor, Biology and Mathematics and Director, Program for Evolutionary Dynamics, Harvard University

Cancer is an evolutionary process. Cancer initiation and progression are caused by somatic mutation and selection of dividing cells. The mathematical theory of evolution can therefore provide quantitative insights into human cancer.

2:40 Refreshment Break in the Exhibit Hall with Poster Viewing

3:25 Close of Conference

Day 1 | Day 2Targeting The Unfolded Protein Response | Download Brochure

Suggested Event Package:

September 21 Short Course: Targeting Protein-Protein Interactions: Biophysical Approaches

September 22-23 Conference: Targeting the Ubiquitin Proteasome System

September 23-24 Conference: Targeting the Unfolded Protein Response