K. Christopher Garcia

Last updated
K. Christopher Garcia
Photo of K. Christopher Garcia, Stanford Faculty.jpg
Alma mater Tulane University, Johns Hopkins University
Scientific career
Fields structural biology
Institutions Stanford University
Doctoral advisor Mario Amzel
Other academic advisors David Goeddel, Tony Kossiakoff, Ian Wilson

K. Christopher Garcia is an American scientist known for his research on the molecular and structural biology of cell surface receptors. Garcia is a professor in the Departments of Molecular and Cellular Physiology and Structural Biology at the Stanford University School of Medicine, [1] an Investigator of the Howard Hughes Medical Institute [2] and a member of the National Academies of Science and Medicine. [3] [4] In addition to his role at Stanford, Garcia is a co-founder of several biotechnology companies, including Alexo Therapeutics, [5] Surrozen, [6] and 3T Biosciences. [7]

Contents

Education

Garcia earned his B.S. in biochemistry from Tulane University. He attended graduate school at the Johns Hopkins University School of Medicine, where he received his Ph.D. in Biophysics under the mentorship of L. Mario Amzel. After receiving his Ph.D., Garcia conducted postdoctoral research at Genentech in the laboratories of David Goeddel and Tony Kossiakoff, where he immersed himself in the nascent technologies of protein engineering and recombinant protein expression, and then at The Scripps Research Institute in the laboratory of Ian Wilson.

Research career

Garcia's research integrates approaches in structural biology, biochemistry and protein engineering to understand how cell surface receptors sense environmental cues through the engagement of extracellular ligands, and transduce signals. The overarching theme of the laboratory is to elucidate the structural and mechanistic basis of receptor activation in systems relevant to human disease, and to exploit this information to design and engineer new molecules with therapeutic properties. Thus there is a close integration of basic science discovery with translation. Garcia's laboratory at Stanford has published numerous scientific articles describing the molecular structure and signaling mechanisms of proteins important for immunity, neurobiology and development. [8] According to data from Google Scholar, Garcia's publication record yields an h-factor of 105 as of February 2023. [9]

Antigen recognition

Garcia's earliest research as a graduate student at Johns Hopkins University focused on understanding how anti-idiotyopic antibodies recognize peptide antigens. [10] As a postdoctoral scholar at The Scripps Research Institute, Garcia conducted a groundbreaking study that revealed how T cells of the immune system survey peptides presented by major histocompatibility complex proteins (MHC), thus allowing them to distinguish between "self" and "non-self". Garcia's research led to the first visualization of a T cell receptor (TCR) bound to a peptide-MHC (pMHC) complex and was published in the journal Science in 1996. [11] Garcia's 1996 article on the TCR-MHC interaction has had broad impact in the fields of immunology and immunotherapy. [12]

At Stanford University, the Garcia Laboratory reported the structure of the pre-B cell receptor (pre-BCR) in 2007, which revealed how pre-BCRs oligomerize to signal in the absence of antigen. [13] Garcia's group has also authored several additional landmark articles exploring various aspects of TCR-pMHC interactions, including the first structure of a γδ TCR-pMHC complex, [14] the molecular basis for dual recognition of "self" and "foreign" MHCs by TCRs, [15] insights into the germline basis of TCR/MHC interactions, [16] [17] the extent of cross-reactivity in the TCR repertoire, [18] [19] and elucidation of the structural trigger for TCR signaling. [20] In Garcia's most recent work, his lab developed a peptide-MHC library technology that has enabled the discovery of antigens for orphan T cell receptors, such as those resident in tumors. This technology also enabled a breakthrough in understanding how signaling is initiated by pMHC engagement.

Cytokine signaling

Garcia's research has established how structural and biophysical principles govern receptor binding and signal activation in many different cytokine systems. Key findings include determination of the first crystal structures of the following cytokine family members in complex with their surface receptors: gp130 family (IL-6), [21] common gamma (γc) family (IL-2), [22] Type I Interferons (IFNα2/IFNω) [23] and Type III Interferons. [24] The Garcia Laboratory has also determined crystal structures of many other major cytokine-receptor complexes including those of IL-1, IL-4, IL-13, IL-15, IL-17, IL-23, LIF and CNTF. These structures have revealed a wide range of binding topologies and architectures, and demonstrate how convergent evolution has provided many solutions for cytokine receptors to transduce signals across the cell membrane. In addition to molecular studies of cytokines, Garcia's group has also used directed evolution to engineer high affinity cytokine variants (IL-2, IL-4, IFN-λ) with improved therapeutic properties. [25] [24] [26]

Wnt signaling

In 2012, Garcia's laboratory determined the crystal structure of a Wnt protein in complex with its cellular receptor, Frizzled. [27] The Wnt-Frizzled structure indicated that Wnts utilize a post-translational lipid modification to directly engage the Frizzled extracellular domain, which represents a highly unusual binding mode among soluble ligands. Garcia's study revealed a striking, donut-shaped architecture adopted by the Wnt-Frizzled complex that adorns the cover of the July 6th, 2012 issue of Science. [27] More recently, Garcia's laboratory reported a breakthrough in being able to recapitulate canonical Wnt signaling using water-soluble bispecific ligands that dimerize Frizzled and Lrp6, which has important implications for the development of therapeutics for regenerative medicine. [28]

Notch signaling

In 2015 and 2017, Garcia published articles in Science describing the first atomic-level visualizations of Notch signaling complexes. [29] [30] Garcia's group used directed evolution to strengthen low-affinity interactions between the receptor Notch1 and ligands Delta-like 4 (DLL4) and Jagged1 (Jag1) as a means of stabilizing the complexes for co-crystallization. Notch1-DLL4 and Notch1-Jag1 structures were determined by x-ray crystallography and revealed long, narrow binding interfaces assisted by multiple O-linked fucose and glucose modifications on Notch1. O-linked glycans are rarely observed at protein-protein interfaces, and their presence at the Notch-ligand interface explained how changes in glycosylation state influence Notch signaling activity. Garcia's 2017 publication also established that Notch-ligand interactions form catch bonds, and that Delta-like and Jagged ligands have different mechanical force thresholds for Notch receptor activation. [30]

GPCR signaling

In 2015, the Garcia Laboratory reported the x-ray crystal structure of the virally encoded G-protein coupled receptor (GPCR), US28, bound to its chemokine ligand, fractalkine (CX3CL1). [31] The US28-Fractalkine structure was one of the first reports to visualize a protein ligand bound to a GPCR, and revealed that the globular "head" of fractalkine docks onto the extracellular loops of US28, while fractalkine's flexible N-terminal "tail" threads into a cavity in the center of US28 as a means of fine-tuning its downstream signaling activity. In more recent studies, the lab has engineered biased chemokine ligands and shown that GPCR activation is governed by ligands that induce shape changes rather than highly specific bonding chemistries. [32]

Cancer immunotherapy

Garcia has conducted several studies targeting cellular receptors for applications in cancer immunotherapy. In 2013, Garcia's group developed high affinity antagonists of the receptor CD47 that potently enhance the antitumor effects of established therapeutic antibodies. [33] Garcia later determined that the therapeutic effects of CD47 blockade require combination therapy with checkpoint blockade antibodies in immunocompetent hosts, thus proving that CD47-based therapy relies upon stimulation of the adaptive immune system. [34] Garcia's lab published the creation of an "orthogonal" IL-2 receptor complex to enable the selective delivery of IL-2 signals to engineered T cells during adoptive cell therapy. [35] They also reported a new technology using yeast-displayed peptide-MHC molecules to identify tumor antigens recognized by Tumor Infiltrating Lymphocytes. [36]

Video highlights

Garcia has published descriptions of several research findings online in the form of videos. [37] [38]

Awards

Personal life

Garcia is a competitive long-distance runner and has run more than 120 ultramarathons, including several 100-mile races.

Related Research Articles

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">T cell</span> White blood cells of the immune system

T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

<span class="mw-page-title-main">Paracrine signaling</span> Form of localized cell signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

<span class="mw-page-title-main">Superantigen</span> Antigen which strongly activates the immune system

Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. Superantigens act by binding to the MHC proteins on antigen-presenting cells (APCs) and to the TCRs on their adjacent helper T-cells, bringing the signaling molecules together, and thus leading to the activation of the T-cells, regardless of the peptide displayed on the MHC molecule. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.

<span class="mw-page-title-main">Notch signaling pathway</span> Series of molecular signals

The Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.

Alloimmunity is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility antigens. In alloimmunity, the body creates antibodies against the alloantigens, attacking transfused blood, allotransplanted tissue, and even the fetus in some cases. Alloimmune (isoimmune) response results in graft rejection, which is manifested as deterioration or complete loss of graft function. In contrast, autoimmunity is an immune response to the self's own antigens. Alloimmunization (isoimmunization) is the process of becoming alloimmune, that is, developing the relevant antibodies for the first time.

<span class="mw-page-title-main">T-cell receptor</span> Protein complex on the surface of T cells that recognizes antigens

The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.

<span class="mw-page-title-main">Immunological synapse</span> Interface between lymphocyte and target cell

In immunology, an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell, B cell, or natural killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.

A thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood.

MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.

<span class="mw-page-title-main">Frizzled-6</span> Protein-coding gene in the species Homo sapiens

Frizzled-6(Fz-6) is a protein that in humans is encoded by the FZD6 gene.

Secretin receptor family consists of secretin receptors regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.

<span class="mw-page-title-main">HLA-F</span> Protein-coding gene in the species Homo sapiens

HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include IFN-gamma signaling and CDK-mediated phosphorylation and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication.

<span class="mw-page-title-main">Signal-regulatory protein alpha</span> Protein-coding gene in the species Homo sapiens

Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.

Mucosal-associated invariant T cells make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B2 and B9 metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease, although definitive evidence is yet to be published.

Artificial antigen presenting cells (aAPCs) are engineered platforms for T-cell activation. aAPCs are used as a new technology and approach to cancer immunotherapy. Immunotherapy aims to utilize the body's own defense mechanism—the immune system—to recognize mutated cancer cells and to kill them the way the immune system would recognize and kill a virus or other micro-organisms causing infectious diseases. Antigen presenting cells are the sentinels of the immune system and patrol the body for pathogens. When they encounter foreign pathogens, the antigen presenting cells activate the T cells—"the soldiers of the immune system"— by delivering stimulatory signals that alert there is foreign material in the body with specific cell surface molecules (epitopes). aAPCs are synthetic versions of these sentinel cells and are made by attaching the specific T-cell stimulating signals to various macro and micro biocompatible surfaces like micron-sized beads. This can potentially reduce the cost while allowing control over generating large numbers of functional pathogen-specific T cells for therapy. Activated and stimulated T cells can be studied in this biomimetic contex and used for adoptive transfer as an immunotherapy.

<span class="mw-page-title-main">CD28 family receptor</span> Group of regulatory cell surface receptors

CD28 family receptors are a group of regulatory cell surface receptors expressed on immune cells. The CD28 family in turn is a subgroup of the immunoglobulin superfamily.

References

  1. ↑ Stanford Medicine Profiles - Chris Garcia
  2. ↑ Howard Hughes Medical Institute Scientists - K. Christopher Garcia
  3. 1 2 Proceedings of the National Academy of Sciences - Member Details, K. Christopher Garcia
  4. 1 2 Press release (2016) - National Academy of Medicine elects 79 new members
  5. ↑ Pitchbook Profile of Alexo Therapeutics
  6. ↑ Yahoo Finance - Surrozen Launches Into Regenerative Medicine
  7. ↑ Farr, Christina (2017-10-04). "Peter Thiel and Sean Parker are financing a secretive cancer-fighting start-up, source says". CNBC. Retrieved 2018-08-28.
  8. ↑ PubMed - articles authored by Garcia, KC
  9. ↑ Google Scholar Citations for K. Christopher Garcia
  10. ↑ Three-dimensional structure of an angiotensin II-Fab complex at 3 A: hormone recognition by an anti-idiotypic antibody, Science (1992)
  11. ↑ An αβ T Cell Receptor Structure at 2.5 Å and Its Orientation in the TCR-MHC Complex, Science (1996)
  12. ↑ Google Scholar citations of "An alpha-beta T cell receptor structure at 2.5 microns and its orientation in the TCRMHC complex"
  13. ↑ Structural Insight into Pre-B Cell Receptor Function, Science (2007)
  14. ↑ Structure of a γδ T Cell Receptor in Complex with the Nonclassical MHC T22, Science (2005)
  15. ↑ Colf, Leremy A.; Bankovich, Alexander J.; Hanick, Nicole A.; Bowerman, Natalie A.; Jones, Lindsay L.; Kranz, David M.; Garcia, K. Christopher (2007). "How a Single T Cell Receptor Recognizes Both Self and Foreign MHC". Cell. 129 (1): 135–146. doi: 10.1016/j.cell.2007.01.048 . PMID   17418792. S2CID   13979698.
  16. ↑ Feng, Dan; Bond, Christopher J.; Ely, Lauren K.; Maynard, Jennifer; Garcia, K. Christopher (September 2007). "Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'". Nature Immunology. 8 (9): 975–983. doi:10.1038/ni1502. ISSN   1529-2908. PMID   17694060. S2CID   9902244.
  17. ↑ Sharon, Eilon; Sibener, Leah V.; Battle, Alexis; Fraser, Hunter B.; Garcia, K. Christopher; Pritchard, Jonathan K. (September 2016). "Genetic variation in MHC proteins is associated with T cell receptor expression biases". Nature Genetics. 48 (9): 995–1002. doi:10.1038/ng.3625. ISSN   1546-1718. PMC   5010864 . PMID   27479906.
  18. ↑ Birnbaum, Michael E.; Mendoza, Juan L.; Sethi, Dhruv K.; Dong, Shen; Glanville, Jacob; Dobbins, Jessica; Özkan, Engin; Davis, Mark M.; Wucherpfennig, Kai W.; Garcia, K. Christopher (2014). "Deconstructing the Peptide-MHC Specificity of T Cell Recognition". Cell. 157 (5): 1073–1087. doi:10.1016/j.cell.2014.03.047. PMC   4071348 . PMID   24855945.
  19. ↑ Lightsources.org Stanford researchers discover immune system's rules of engagement
  20. ↑ Sibener, Leah V.; Fernandes, Ricardo A.; Kolawole, Elizabeth M.; Carbone, Catherine B.; Liu, Fan; McAffee, Darren; Birnbaum, Michael E.; Yang, Xinbo; Su, Laura F. (2018-07-26). "Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding". Cell. 174 (3): 672–687.e27. doi:10.1016/j.cell.2018.06.017. ISSN   1097-4172. PMC   6140336 . PMID   30053426.
  21. ↑ Hexameric Structure and Assembly of the Interleukin-6/IL-6 α-Receptor/gp130 Complex, Science (2003)
  22. ↑ Structure of the Quaternary Complex of Interleukin-2 with Its α, ß, and γc Receptors, Science (2005)
  23. ↑ Thomas, Christoph (2011). "Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons". Cell. 146 (4): 621–632. doi:10.1016/j.cell.2011.06.048. PMC   3166218 . PMID   21854986.
  24. 1 2 The IFN-λ-IFN-λR1-IL-10Rβ Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity, Immunity (2017)
  25. ↑ Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'
  26. ↑ Junttila, Ilkka S.; Creusot, Remi J.; Moraga, Ignacio; Bates, Darren L.; Wong, Michael T.; Alonso, Michael N.; Suhoski, Megan M.; Lupardus, Patrick; Meier-Schellersheim, Martin (December 2012). "Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines". Nature Chemical Biology. 8 (12): 990–998. doi:10.1038/nchembio.1096. ISSN   1552-4469. PMC   3508151 . PMID   23103943.
  27. 1 2 Structural basis of Wnt recognition by Frizzled, Science (2012)
  28. ↑ Janda, Claudia Y.; Dang, Luke T.; You, Changjiang; Chang, Junlei; de Lau, Wim; Zhong, Zhendong A.; Yan, Kelley S.; Marecic, Owen; Siepe, Dirk (2017-05-11). "Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling". Nature. 545 (7653): 234–237. doi:10.1038/nature22306. ISSN   1476-4687. PMC   5815871 . PMID   28467818.
  29. ↑ Structural basis for Notch1 engagement of Delta-like 4, Science (2015)
  30. 1 2 Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity
  31. ↑ Structural basis for chemokine recognition and activation of a viral G protein–coupled receptor, Science (2015)
  32. ↑ Miles, Timothy F.; Spiess, Katja; Jude, Kevin M.; Tsutsumi, Naotaka; Burg, John S.; Ingram, Jessica R.; Waghray, Deepa; Hjorto, Gertrud M.; Larsen, Olav (2018-06-08). "Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy". eLife. 7. doi: 10.7554/eLife.35850 . ISSN   2050-084X. PMC   5993540 . PMID   29882741.
  33. ↑ Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies, Science (2013)
  34. ↑ Durable antitumor responses to CD47 blockade require adaptive immune stimulation, PNAS (2016)
  35. ↑ Sockolosky, Jonathan T.; Trotta, Eleonora; Parisi, Giulia; Picton, Lora; Su, Leon L.; Le, Alan C.; Chhabra, Akanksha; Silveria, Stephanie L.; George, Benson M. (2018-03-02). "Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes". Science (Submitted manuscript). 359 (6379): 1037–1042. doi:10.1126/science.aar3246. ISSN   1095-9203. PMC   5947856 . PMID   29496879.
  36. ↑ Gee, Marvin H.; Han, Arnold; Lofgren, Shane M.; Beausang, John F.; Mendoza, Juan L.; Birnbaum, Michael E.; Bethune, Michael T.; Fischer, Suzanne; Yang, Xinbo (2018-01-25). "Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes". Cell. 172 (3): 549–563.e16. doi:10.1016/j.cell.2017.11.043. ISSN   1097-4172. PMC   5786495 . PMID   29275860.
  37. ↑ Cell Press (2011-08-03), Interferons—Provoking Distinct Signals through the Same Receptor , retrieved 2018-09-19
  38. ↑ Cell Press (2014-01-16), "Extracellular Architecture of the SYG-1/SYG-2 Adhesion Complex Instructs Synaptogenesis", Cell, 156 (3): 482–494, doi:10.1016/j.cell.2014.01.004, PMC   3962013 , PMID   24485456 , retrieved 2018-09-19
  39. ↑ Rita Allen Foundation
  40. ↑ Pew Trusts
  41. ↑ Philanthropy News Digest
  42. ↑ Passano Foundation Award 2024
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