Kristin Baldwin, PhD

Investigator, Dorris Neuroscience Center
Adjunct Professor, Ucsd Neuroscience
Department of Neuroscience
California Campus


Scripps Research Joint Appointments

Dorris Neuroscience Center
Faculty, Graduate Program

Other Joint Appointments

Adjunct Associate Professor, Department of Neurosciences, University of California San Diego

Research Focus

Advancing Stem Cell Technology to Study Genomes and the Brain:

Generating Mice from iPS Cells: During development, undifferentiated stem cells generate the millions of distinct cell types in the body in a choreographed sequence that is unidirectional. Until recently, differentiated mammalian cells were thought to have irreversibly lost the ability to generate less differentiated cell types, for unknown reasons. Thus embryonic stem cells and somatic stem cells were assumed to be unique resources to generate more differentiated cell types in vitro. Reprogramming by transient expression of pluripotency factors can restore differentiated cells to a state of developmental potency that resembles embryonic stem (ES) cells, however, the first generations of induced pluripotent stem (iPS) cells differed from ES cells in that they could not generate live adult mice. We recently developed a reprogramming method that restores differentiated fibroblasts to full pluripotency such that we can produce live mice derived entirely from differentiated cells, without using oocytes. These fully pluripotent iPS cells and iPS mice allow us to examine the functional stability of iPS-derived tissues and to probe the genomic stability of differentiated cells. Applying this technology to human cells should allow us to generate improved iPS cell lines. One goal is to use these cells to generate improved models of disease, in particular, inherited human neurological diseases for which no in vitro models exist.

Control of genome stability during reprogramming and in iPSCs: Reprogramming by the cytoplasm of the egg, or by direct expression of transcription factors requires genome-wide remodeling of DNA. This occurs by mechanisms that are poorly understood. Recent studies in human iPS cells suggested that these cells may necessarily harbor increased numbers of mutations compared to ES cells. We recently performed whole genome sequencing on several mouse iPSC lines that have been shown to be fully reprogrammed because they can generate fertile adult mice. In contrast to the reports of others, we find a very low burden of genomic structural changes in these lines. This shows that reprogramming need not be highly mutagenic and opens the door to identifying methods to produce iPS cell lines with minimal genome instability. In addition, we identified some mutations that arose in the donor cell lineage during somatic differentiation. This result, combined with the low mutation rate we observed will allow us to use reprogramming to identify the source and scope of somatic mutations arising in different tissues and identify optimal tissue sources for human iPS cell lines.

Generating Cell Lines from Neurons: Brains are composed of an extraordinary diversity of neurons, which are primarily generated at birth and are maintained without cell division for the life of an individual. Neurons do not divide and have not been shown to generate tumors, for unknown reasons. The inability to generate cell lines from neurons precludes a number of important studies including analyses of neuronal genomic stability in differentiation and disease, and has impeded the generation of appropriate in vitro models of disease. Previously we were the first to generate cloned mice and ES cell lines from differentiated olfactory sensory neurons using reprogramming by nuclear transfer. A current goal is to generate cell lines from neurons to identify unknown irreversible changes to neuronal DNA and to generate the best possible models of neurological diseases such as autism, schizophrenia, Parkinson’s disease and developmental diseases arising from inherited defects in genome maintenance and epigenetic alterations.

Modeling Neurological Disease Using Reprogramming: Reprogramming may be used to generate neurons in vitro in two ways. First, non-neuronal tissues from mice or humans affected with a particular disease may be reprogrammed to pluripotency and the resulting iPSCs or SCNT-ESCs may be subsequently differentiated into cells of the neural lineage. This approach may be useful for modeling neurodevelopmental diseases – from rare inherited monogenic disorders to more common disorders such as autism or schizophrenia. A second approach is to directly reprogram skin cells or other lineages to neurons without transiting through any precursor states using transcription factors or microRNAs. Our laboratory is exploring the capabilities and limitations of both approaches using mouse and human models.

Generating Neuronal Diversity and Connectivity in the Olfactory System. Exciting recent advances in stem cell technology that suggest it may be possible to generate neurons in vitro to model disease or for use in cell replacement therapy. However, little is known about the extent of genetic diversity of neurons of the same subtype, or how diverse neurons are wired together to form a functional neuronal circuit. We exploit the genetic tractability and anatomic stereotypy of the olfactory system to generate gene targeted mice in which we can label and modify specific neuronal circuits involved in detecting smells. We are currently mapping the links between the nose and cortical brain regions involved in responding to odors. Identifying the patterns of gene expression and synaptic connectivity of defined neuronal populations will be important to assess the potential utility of iPS derived neurons in vitro and in transplantation experiments and should shed light on design principles of functional neuronal circuits.


Ph.D. (Immunology), Stanford University, Department of Microbiology and Immunology, Howard Hughes Medical Institute, 1998
B.A. (Economics), Duke University, 1991
B.S. (Zoology), Duke University, 1991

Professional Experience

2017-2017 Associate Professor, Neuroscience, Scripps Research
2013-2017 Associate Professor, Molecular and Cellular Neuroscience (MCN), Scripps Research
2011-2012 Associate Professor, Cell Biology, Scripps Research
2006-2011 Assistant Professor, Cell Biology, Scripps Research
2003-2005 Associate Research Scientist with Dr. Richard Axel, Columbia University
1998-2003 Postdoctoral Research Fellow with Dr. Richard Axel, Columbia University
1997-1998 Postdoctoral Fellow with Dr. Mark M. Davis, Stanford University

Awards & Professional Activities

2016 NIH Director's Pioneer Award

2012                 Kavli Fellow and Session Chair, Kavli Frontiers of Science Symposium

2011 – 2012      Donald E. and Delia B. Baxter Foundation Faculty Scholar

2008 - 2012      CIRM New Faculty Awardee

2007 – 2011      Pew Scholar in the Biological Sciences

2007 – 2010      Whitehall Grant Award


Selected References

All Publications

  1. Tsunemoto RK, Lee, S, Szűcs A, Chubukov P, Sokolova I, Blanchard JW, Eade KT, Bruggemann J, Wu C, Torkamani A, Sanna PP, Baldwin, KK.  Diverse reprogramming codes for neuronal identity. Nature. 2018 May;557 (7705):375-380. PMID: 29743677

Blanchard JW, Xie J, El-Mecharrafie N, Gross S, Lee S, Lerner RA, Baldwin KK. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries.  Nature Biotechnol. 2017 Sep 11. doi: 10.1038/nbt.3963. [Epub ahead of print] PMID: 28892074

Lo Sardo V, Ferguson W, Erikson GA, Topol EJ, Baldwin KK#, Torkamani A#. Influence of donor age on induced pluripotent stem cells. Nature Biotechnol. 2017 Jan;35(1):69-74. doi: 10.1038/nbt.3749. PMID: 27941802.# equal contribution, co-corresponding authors

*Hazen, J.L., Faust, G.G., Rodriguez, A.R. Ferguson1, W.C. Shumilina. S., Clark. R.A.2, Boland. M.J.1, Martin, G., Chubukov, P., Tsunemoto, R. K. Torkamani, A., Kupriyanov, S., Hall, I.M. and Baldwin, K.K. The complete genome sequences, unique mutational spectra and developmental potency of adult neurons revealed by cloning. Neuron, 2016 Mar 16;89(6):1223-36. PMID:26948891

Hiler D, Chen X, Hazen J, Kupriyanov S, Carroll PA, Qu C, Xu B, Johnson D, Griffiths L, Frase S, Rodriguez AR, Martin G, Zhang J, Jeon J, Fan Y, Finkelstein D, Eisenman RN, Baldwin K, Dyer MA. Quantification of Retinogenesis in 3D Cultures Reveals Epigenetic Memory and Higher Efficiency in iPSCs Derived from Rod Photoreceptors. Cell Stem Cell. 2015 Jul 2; 17(1): 101-15. PMID: 26140606

Nityanandam A, Baldwin KK. Advances in reprogramming based study of neurologic disorders. Stem Cells Dev. 2015 Jun 1;24(11):1265-83. Review. PMID: 25749371

Tsunemoto RK, Blanchard JW, Eade KT, Baldwin KK. Engineering neuronal diversity using direct reprogramming. EMBO, 2015 Jun 3; 34(11):1445-1455. Review. PMID: 25908841

*Blanchard JW, Eade KT, Szűcs A, Lo Sardo V, Tsunemoto RK, Williams D, Sanna PP, Baldwin KK. Selective conversion of fibroblasts into peripheral sensory neurons. Nat Neurosci. 2015 Jan;18(1):25-35. doi: 10.1038/nn.3887. Epub 2014 Nov 24. PMID: 25420069 

Boland, M.J., Hazen, J.L., Nazor, K.L., Rodriguez, A.R., Martin, G., Kupriyanov, S., Baldwin, KK. Generation of Mice Derived from Induced Pluripotent Stem Cells. J. Vis. Exp. 2012 Nov. 29 (69), e4003, doi:10.3791/4003


*Quinlan, AR, *Boland, MJ, Leibowitz, ML, Shumilina, S., Pehrson, SM, *Baldwin, KK, and *Hall, IM. Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell. 2011 Oct 4;9(4):366-73.* equal contribution PMID: 21982236

Ghosh, S., Larson, S., Hefzi, H., Marnoy, Z., Cutforth, T., Dokka, K., and Baldwin, KK. Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons. Nature. 14 April 2011; 472(7342):217-20. PMID: 21451523

Boland, MJ*, Hazen, JL*, Nazor KL*, Rodriguez AR, Gifford W, Martin G, Kupriyanov S, and Baldwin KKAdult mice generated from induced pluripotent stem cells.  Nature, 03 September 2009; 46:91-96. PMID: 19672243 * equal contribution


Lab Website

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