Fangfang Shen is a postdoc scholar in Laura Dassama lab at the Department of Chemistry. She received her B.S. in Biology and M.S. in Organic Chemistry at Lanzhou University. Before joined Stanford University in Jan 2020, she obtained her Ph.D. at The University of Hong Kong, where her research focused on the development of small molecules to mimic protein functions and their applications as anti-cancer drugs. Currently, her research interest is the identification of novel protein inhibitors as new therapies for blood disorders, including sickle cell disease and beta-thalassemia.
Bachelor of Science, Lanzhou University (2010)
Master of Science, Lanzhou University (2013)
PhD, The University of Hong Kong, Chemical biology (2018)
Laura Dassama, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
Identify protein inhibitors and develop novel specific protein delivery systems.
A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin.
ACS central science
2022; 8 (12): 1695-1703
Proximity-based strategies to degrade proteins have enormous therapeutic potential in medicine, but the technologies are limited to proteins for which small molecule ligands exist. The identification of such ligands for therapeutically relevant but "undruggable" proteins remains challenging. Herein, we employed yeast surface display of synthetic nanobodies to identify a protein ligand selective for BCL11A, a critical repressor of fetal globin gene transcription. Fusion of the nanobody to a cell-permeant miniature protein and an E3 adaptor creates a degrader that depletes cellular BCL11A in differentiated primary erythroid precursor cells, thereby inducing the expression of fetal hemoglobin, a modifier of clinical severity of sickle cell disease and β-thalassemia. Our strategy provides a means of fetal hemoglobin induction through reversible, temporal modulation of BCL11A. Additionally, it establishes a new paradigm for the targeted degradation of previously intractable proteins.
View details for DOI 10.1021/acscentsci.2c00998
View details for PubMedID 36589886
View details for PubMedCentralID PMC9801508
Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule.
Journal of the American Chemical Society
2020; 142 (24): 10769-10779
Molecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K+ transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K+/H+ transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K+ channels.
View details for DOI 10.1021/jacs.0c02134
View details for PubMedID 32441923
A small synthetic molecule functions as a chloride-bicarbonate dual-transporter and induces chloride secretion in cells
2016; 52 (46): 7380–83
A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers.
View details for DOI 10.1039/c6cc01964a
View details for Web of Science ID 000378003100013
View details for PubMedID 27188496
Catalytic Asymmetric 1,2-Addition of alpha-Isothiocyanato Phosphonates: Synthesis of Chiral beta-Hydroxy- or beta-Amino-Substituted alpha-Amino Phosphonic Acid Derivatives
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2014; 53 (7): 1862–66
α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.
View details for DOI 10.1002/anie.201308514
View details for Web of Science ID 000330680400020
View details for PubMedID 24420101
- Catalytic Enantioselective Ring-Opening Reaction of meso-Aziridines with -Isothiocyanato Imides CHEMISTRY-A EUROPEAN JOURNAL 2013; 19 (29): 9476–80
- Catalytic Asymmetric Michael Addition/Cyclization of Isothiocyanato Oxindoles: Highly Efficient and Versatile Approach for the Synthesis of 3,2'-Pyrrolidinyl Mono- and Bi-spirooxindole Frameworks CHEMISTRY-A EUROPEAN JOURNAL 2013; 19 (4): 1184–88
- Enantioselective Michael/Cyclization Reaction Sequence: Scaffold-Inspired Synthesis of Spirooxindoles with Multiple Stereocenters ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2011; 50 (39): 9124–27
A Unique Approach to the Concise Synthesis of Highly Optically Active Spirooxazolines and the Discovery of a More Potent Oxindole-Type Phytoalexin Analogue
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2010; 132 (43): 15328–33
Drug-lead synthesis through rapid construction of chiral molecular complexity around the biologically relevant framework using a highly efficient strategy is a key goal of organic synthesis. Molecules bearing a spirooxindole-type framework exhibit important bioactivities. Herein, we present a highly efficient and convenient strategy that allows rapid construction of unique optically active spiro[oxazoline-3,3'-oxindole]s through the organocatalyzed asymmetric synthesis of spirocyclic thiocarbamates via an aldol reaction. Preliminary biological evaluation of several of the spirooxazolines using a model of acute neuroinflammation revealed promising antipyretic activity and provided an opportunity to discover new antipyretic agents.
View details for DOI 10.1021/ja106349m
View details for Web of Science ID 000283621700046
View details for PubMedID 20939568
Direct Organocatalytic Asymmetric Aldol Reaction of alpha-Isothiocyanato Imides to alpha-Ketoesters under Low Ligand Loading: A Doubly Stereocontrolled Approach to Cyclic Thiocarbamates Bearing Chiral Quaternary Stereocenters
2010; 12 (7): 1544–47
The first doubly stereocontrolled organocatalytic asymmetric aldol reaction of alpha-isothiocyanato imides with alpha-ketoesters by using rosin-derived tertiary amine-thiourea under low ligand loading to form cyclic thiocarbamates bearing quaternary stereogenic centers with high levels of enantio- and diastereoselectivity (up to 99% ee, and 97:3 dr) is presented. This reaction provides a convenient doubly stereocontrolled method to access synthetic useful multiply substituted cyclic thiocarbamates with high optical purity.
View details for DOI 10.1021/ol1002829
View details for Web of Science ID 000275885400043
View details for PubMedID 20205429