Professor David S. Eisenberg
Post Doctoral Fellows
As a postdoctoral researcher at UCLA, I am in charge of planning and executing a fundamental science research program to understand biochemical processes of systemic amyloidosis disease, and build a foundation for development of a possible cure of the disease in future. Amyloidosis develops due to assembly of light-chain immunoglobulins into a protein polymer, known as amyloid fibrils. These fibrils possess a special biochemical properties preventing their clearance from the body, eventually leading to essential organs failure and death.
Recent research had shown that propagation of amyloid fibrils is mediated by a discrete, naturally occurring short peptide segments with a high propensity to assemble into insoluble beta-sheet structures. With a goal of illuminating the structural basis of systemic amyloidosis, I hypothesized that such peptide segments exist in immunoglobulin light-chains. In concordance with this hypothesis, I identified several peptide segments within lambda type immunoglobulins that induce formation of amyloid-like structures. Currently, I use a site-directed mutagenesis methods to assess the structural necessity of these peptide segments to light-chain immunoglobulin amyloidogenic potential, in hope to use this data for development of molecules that will disrupt amyloid formation, which is the ultimate long term goal of our research.
My research aims to find a link between the structure and toxicity of protein aggregates in the amyloid diseases. I am examining the toxicity of amyloid protein fragments to cultured human cells, trying to answer: "Are there sequence features of amyloid fragments that give clues about their toxic structure?"
I am a postdoc in Eisenberg’s lab and my research here mostly focuses on the interaction between Amyloid beta (Aβ) and its binders (binding proteins/small molecules). My goal is to solve the crystal structure of binder stabilized Aβ (or Aβ derived peptides), or developing Aβ inhibitors from these binding protein/small molecules.
Jose Rodriguez works to solve the structures of protein segments that form amyloid. These segments form small crystals. Too small to extract information from them by conventional methods. Instead, Jose solves their structures using advanced x-ray and electron sources, and frontier techniques in crystallography and structural biology. Uncovering how and why amyloid deposits form and what their atomic structures look like could teach us about how they cause disease. Their structures are a starting point to the design and production of drugs that could prevent or reduce the deadly effects of amyloid disease.
I am working on determining structures of Tau oligomers and amyloid fibers that are involved in Alzheimer’s disease and other tauopathies. Through these studies I hope to uncover the structural basis of toxicity and seeding, as well as to understand how certain Tau structures might protect against disease. Additionally I am working with Lin Jiang to develop inhibitors that block Tau fibrillization based on structures that our group has solved.
My professional goal is to contribute to the understanding of the molecular basis of amyloid-related diseases from a structural point of view, in order to design effective and safe potential peptide therapeutics. Recent studies in collaboration with the Department of Chemistry and Applied Bioscience at ETH Zürich have resulted in the design and assessment of successful peptide inhibitors of protein aggregation for Alzheimer’s disease and transthyretin amyloidosis. For my research, I combine structural analysis of amyloid protein segments and intact proteins with molecular and cell biology to test toxicity inhibition of our designs.
Alice focuses on p53 aggregation in cancer. She developed a peptide therapeutic that arrests p53 aggregation and restores its tumor suppressor function in cancer cells.
She is also interested in studying eosinophils and protein aggregation in the context of the innate immune response.
I‘m Meng Zhang, a Postdoc at David Eisenberg’s lab. My research goal is to figure out the segments which initiate the aggregation of alpha synuclein protein, and understand the structures of alpha synuclein in fibrils and oligomers.
My research focuses on determining the molecular structures of Amyloid Beta (Aβ), the protein responsible for Alzheimer’s Disease. Aβ is observed as multiple aggregated structures including amyloid fibrils, smaller protofibrils, as well as oligomeric species which are associated with higher toxicities. By determining the structures of the distinct species, I hope to identify what features are responsible for Aβ toxicity. To this end, I have focused on familial mutations in Aβ which alter the structure and contribute to heightened toxicity and early onset of the disease.
Amyloid proteins are traditionally associated with neurodegenerative diseases like Alzheimer’s Disease, Parkinson’s Disease, and ALS. A hallmark of pathology from these neurodegenerative diseases is the presence of extraordinarily stable amyloid fibrils. Recently the McKnight lab has indicated that many RNA binding proteins with Low-Complexity (LC) domains such as FUS, TDP43, and hnRNPA2 can form a hydrogel composed of amyloid-like fibrils. LC domain oligomerization into fibrils is linked to important cellular functions; specifically stress granule formation. Unlike amyloid fibrils from neurodegenerative diseases, these hydrogel-forming amyloid fibrils are more labile. I study structure of segments from LC domains thought to be important for their fibril formation to identify structural features that may mediate their inherent lability relative to other amyloid fibrils.
My research focuses on understanding the aggregation of TAR DNA Binding Protein 43, TDP-43, an amyloid protein implicated in Amyotrophic Lateral Sclerosis and other neurodegenerative diseases. I am interested in understanding how TDP-43 can form reversible aggregates in the form of stress granules as well as irreversible aggregates in the form of pathological deposits of diseases. I utilize a number of different techniques including X-ray crystallography, electron microscopy, SDS sensitivity assays, cellular toxicity assays and antibody binding to understand the fragments that are important for aggregation. Additionally, I have collaborated on a number of other projects in our lab including work on the proteins alpha-synuclein and SOD-1.
I am interested in the structures formed by Human Islet Amyloid Polypeptide (hIAPP) in the world’s most common amyloid disease, Type II Diabetes. I have used frontier structure determination methods, like Micro-Electron Diffraction, to solve structures of segments that form the amyloid spine of hIAPP. I have used cell culture models to determine which of these structures represent the toxic core of hIAPP. In collaboration with others in the lab, I am using our model of the toxic core to develop inhibitors using structure-based design.
I am working on deciphering the structural basis of cytotoxicity associated with SOD1, a protein implicated in ALS. I am also collaborating with other members of the group to test aggregation inhibitors of Amyloid Beta (Aβ) and Alpha Synuclein, proteins associated with Alzheimer‘s and Parkinson’s disease.
I help people to determine and analyze interesting macromolecular structures by crystallography. I assist with data collection, data processing, phasing, model building and structure interpretation, and teach others about these techniques.
As Laboratory Manager, my job fluctuates. I keep the lab running, at the level of ordering supplies, equipment, and performing or ordering repairs. I do some of the equipment training. I am Safety Representative for the Eisenberg lab. When I can, I lend technical advice for lab work and occasionally for crystallography.
There is a basic need to understand how proteins are involved in both normal and abnormal cellular processes. To understand how these proteins function at the molecular level, the detailed atomic structure is needed. The knowledge of the three-dimensional structures of proteins provides information upon which we can initiate new molecular, biological, biochemical, protein engineering and drug design efforts. My long-term goal is to provide state-of-the-art resources to researchers in the laboratory, enabling the detailed 3-D analysis of biological macromolecules that play essential roles in human health. I train students and postdocs to use sophisticated equipment and technologies. I also offer advice and technical assistance in sample preparation, crystallization, data collection, processing, atomic refinement and modelling.
Boston University Class of 2014, BA in Chemistry, minor in Mathematics
Woodland Hills, CA
University of California, Riverside