• S.B. Brain and Cognitive Sciences, S.B. Biology, Massachusetts Institute of Technology (2006)
• Ph.D. Biological and Biomedical Sciences, Harvard University (2013)
• Postdoctoral Fellowship, Division of Genetics and Genomics, Children’s Hospital Boston and Harvard Medical School (2016)
• Postdoctoral Fellowship, Department of Ophthalmology, Stanford University (2023)

Courses Taught

• FYS 505 STEM Scholars
• NRSC 160 Introduction to Neuroscience
• NRSC 311 The Hypothalamus
• NRSC 325 Neural Development
• NRSC 334 Medical Genetics
• NRSC 335 Degeneration and Regeneration of the Nervous System
• NRSC s22 Methods in Developmental Neuroscience

Research Interests

Vision loss is a devastating medical problem that leads to lower quality of life and loss of independence among those affected. Because the human retina has minimal or no regenerative ability, the death of retinal neurons due to injury or disease is generally irreversible, making this the most common cause of permanent visual impairment. If retinal neurons could be regenerated from progenitor cells that live within the adult human body, these patients could have their vision restored.

I study the development of retinal ganglion cells, the neurons that connect the eye with the brain. These neurons are vulnerable to injury in traumatic optic nerve injuries and to diseases such as glaucoma, and a deeper understanding of their development and regeneration could have significant implications for reversing visual impairment. I investigate retinal ganglion cells through the lens of development, by seeking to understand the way retinal ganglion cells normally develop and the ways these developmental pathways could be exploited to encourage regeneration in adult animals, using mice as a model system.

Selected Publications

1. Cameron EG, Nahmou M, Toth AB, Heo L, Tanasa B, Dalal R, Yan W, Nallagatla P, Xia X, Hay S, Knasel C, Stile TL, Douglas C, Atkins M, Sun C, Ashouri M, Bian M, Chang KC, Russano K, Shah S, Woodworth MB, Galvao J, Nair RV, Kapiloff MS, Goldberg JL. “A molecular switch for neuroprotective astrocyte reactivity.” (2024) Nature 626, 574-582. PMID: 38086421
2. Woodworth MB, Greig LC, Goldberg J. (2023) “Intrinsic and induced neuronal regeneration in the mammalian retina.” Antioxidants and Redox Signaling 39(16-18): 1039-1052. PMID: 37276181.
3. Woodworth MB, Girskis K, Walsh CA. (2017) “Building a lineage from single cells: Genetic techniques for cell lineage tracking.” Nature Reviews Genetics 18(4): 230-244. PMID: 28111472. With cover.
4. Greig LC*, Woodworth MB*, Greppi C, Macklis JD. (2016) “Ctip1 controls acquisition of sensory area identity and establishment of sensory input fields in the developing neocortex.” Neuron 90(2):261-277. PMID: 27100196. *equal contribution
5. Woodworth MB*, Greig LC*, Liu KX, Ippolito GC, Tucker HO, Macklis JD. (2016) “Ctip1 regulates the balance of projection neuron subtype specification in deep cortical layers.” Cell Reports 15(5): 999-1012. PMID: 27117402. With cover. *equal contribution
6. Lodato MA*, Woodworth MB*, Lee S*, Evrony GD, Mehta BK, Karger A, Lee S, Chittenden TW, D’Gama AM, Cai X, Luquette LJ, Lee E, Park PJ, Walsh CA. (2015) “Somatic mutation in single human neurons tracks developmental and transcriptional history.” Science 350(6256):94-8. PMID: 26430121. With cover. *equal contribution
7. Greig LC*, Woodworth MB*, Galazo MJ, Padmanabhan H, Macklis JD. (2013) “Molecular logic of neocortical projection neuron specification, development, and diversity.” Nature Reviews Neuroscience 14(11): 755-69. PMID: 24105342. *equal contribution
8. Woodworth MB*, Custo Greig L*, Kriegstein AR, Macklis JD. (2012) “Snapshot: Cortical development.” Cell 151(4): 918-918.e.1. PMID: 23141546. *equal contribution

• B.A. Psychology, Rutgers University (2014)
• M.A. Psychology, University of Pennsylvania (2015)
• Ph.D. Neuroscience, Baylor College of Medicine (2020)
• Postdoctoral Fellowship, Department of Psychology, Princeton University (2023)

Courses Taught

• NRSC/PSYC 363 Physiological Psychology/Lab
• NRSC 225 Neuroscience of Video
• FYS 567A What Makes Up Your Mind: Neurocognitive Factors in Decision Making and Control
• NRSC/PSYC 330 Cognitive Neuroscience / Lab

Research Interests

Many of us take for granted the ability to act out our motor plans, but few of us ever achieve the degree of skill mastery that our society exalts in musicians and star athletes. What are the neural and cognitive processes that allow us to attain this degree of expertise? And what goes on during neurological degeneration and disease to undermine our motor systems and make the activities of daily living (e.g., eating, dressing, etc.) difficult or impossible.

Broadly speaking, my research program aims to identify and explore the neural and cognitive processes that give rise to this great diversity of human motor skill and experience. To this end, my work interrogates the processes that support motor control and learning, ranging from implicit mechanisms that automatically calibrate our movements to explicitly-generated plans that we use to overcome obstacles that we recognize in the environment. This research relies on participation from undergraduate students here at �ֲ���ý, people in the general population, and folks with neurological disease, who all contribute to building representative datasets that can speak to motor performance and learning in health and disease.

My dissertation work focused on mechanisms of learning in the cerebellum, which contributes to motor control and emotion regulation, among other processes. Much of my work is informed by theories of error-based, cerebellar learning, and I have ongoing research projects focused on understanding ways that movement is and is not impaired during spinocerebellar ataxia. I am also conducting research that aims to help us better understand and detect Functional Movement Disorder.

Keywords: cerebellum, learning, memory, adaptation, planning, implicit and explicit awareness

Publications

1. Al-Fawakhiri N, Ma A, Taylor JA, & Kim OA (2023). Exploring the role of task success in implicit motor adaptation. Journal of Neurophysiology.
2. Kim OA, Forrence AD, & McDougle SD (2022). Motor learning without movement. Proceedings of the National Academy of Sciences, 119(30).
3. Achilly NP, He L, Kim OA, Ohmae S, Wojaczynski GJ, Lin T, Sillitoe RV, Medina JF, & Zoghbi HY. (2021) Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice. eLife.
4. Kim OA, Ohmae S, & Medina JF. (2020). A cerebello-olivary signal for negative prediction error is sufficient to cause extinction of associative motor learning. Nature Neuroscience, 23.
5. Heiney SA, Ohmae S, Kim OA, Medina JF (2017). Single-unit extracellular recording from the cerebellum during eyeblink conditioning in head-fixed mice. In: Sillitoe, R. (eds) Extracellular Recording Approaches. Neuromethods, vol 134. Humana Press, New York, NY.
6. Barker DJ, Striano BM, Coffey KC, Root DH, Pawlak AP, Kim OA, Kulik J, Fabbricatore AT, & West MO (2015). Sensitivity to self-administered cocaine within the lateral preoptic-rostral lateral hypothalamic continuum. Brain Structure and Function, 220.

I am a Maine native, and grew up on a rural farm in the western mountains. I originally attended culinary arts school and after years of working in the food service industry, I decided to pursue my original interest – biology. I study how aging changes the brain and how those changes can predispose some people to develop neurological diseases such as Parkinson’s disease or Alzheimer’s disease. I use a wide variety of techniques to explore how some people’s protective genes are turned off during aging, and identified a new type of cell in the brain that only shows up in people at risk for neurological diseases.

Selected Publications

*Denotes Undergraduate Authors

Adams L, Song MK, Tanaka Y, Kim YS. Single-nuclei paired multiomic analysis of young, aged, and Parkinson’s disease human midbrain reveals age- and disease-associated glial changes and their contribution to Parkinson’s disease (Current under review). Preprint: doi: https://doi.org/10.1101/2022.01.18.22269350.

Guhathakurta S, Adams L, Jeong I, Sivakumar A*, Cha M*, Bernardo Fiadeiro M*, Hu HN, Kim YS. Precise epigenomic editing with a SunTag-based modular epigenetic toolkit. Epigenetics. 2022 Aug 3:1-7. doi: 10.1080/15592294.2022.2106646.

Song MK, Adams L, Lee JH, Kim YS. NXP031 prevents dopaminergic neuronal loss and oxidative damage in the AAV-WT-α-synuclein mouse model of Parkinson’s disease. PLoS One. 2022 Jul 28;17(7):e0272085. doi: 10.1371/journal.pone.0272085.

Jandy M, Noor A*, Nelson P*, Dennys CN, Karabinas IM*, Pestoni JC*, Singh GD*, Luc L*, Devyldere R, Perdomo N, Mitchell CE, Adams L, Fuse MA, Mendoza FA, Marean-Reardon CL, Mehl RA, Estevez AG, Franco MC. Peroxynitrite nitration of Tyr 56 in Hsp90 induces PC12 cell death through P2X7R-dependent PTEN activation. Redox Biol. 2022 Apr;50:102247. doi: 10.1016/j.redox.2022.102247.

Guhathakurta S, Kim J, Adams L, Basu S, Song MK, Adler E*, Je G, Fiadeiro MB*, Kim YS. Targeted attenuation of elevated histone marks at SNCA alleviates α-synuclein in Parkinson’s disease. EMBO Mol Med. 2021 Feb 5;13(2):e12188. doi: 10.15252/emmm.202012188.

Basu S, Adams L, Guhathakurta S, Kim YS. A novel tool for monitoring endogenous alpha-synuclein transcription by NanoLuciferase tag insertion at the 3’end using CRISPR-Cas9 genome editing technique. Sci Rep. 2017 Apr 4;8:45883. doi: 10.1038/srep45883.

Adams L, Franco MC, Estevez AG. Reactive nitrogen species in cellular signaling. Exp Biol Med (Maywood). 2015 Jun;240(6):711-7. doi: 10.1177/1535370215581314.

• Diploma (equivalent to B.S. & M.S.), Biochemistry & Molecular Biology, University of Hamburg (2004)
•  Philosophiae Doctor, Chemistry, University of Hamburg (2009)
•  Postdoctoral Fellowship, Department of Physiology & Biophysics, University of Washington (2010)

Courses Taught

•  BI/NS 308 Neurobiology / Lab
•  BIO 202 Cellular & Molecular Biology
•  BIO 321 Cellular Biochemistry
•  BIO 473 Seminar and Research in Cell Biology
•  BIO 460 Junior Seminar
•  BI/NS 305 Gene Editing in Biology and Neuroscience
•  BIO 195 Lab-Based Biological Inquiry: Cellular Neuroscience
•  FYS 497 Community Science of Brain Injury in Sports

Research Interests

Over the last decade phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂), a minor membrane phospholipid of the phosphoinositide family, has emerged as a key regulator of nerve cell activity. PI(4,5)P₂ interaction with voltage-gated ion channels is essential for a large number of these channels. In addition, PI(4,5)P₂ is critically involved in exo- and endocytosis, influencing neurotransmitter release and reuptake. A fundamental problem is how neurons accurately control PI(4,5)P₂ levels, and quickly and reversibly adjust them to an altered physiological situation. However, despite the importance of phosphoinositides for the regulation of neuronal activity, little is known about how the metabolism of phosphoinositides is regulated in cells of the nervous system. To address this question, my research focuses on two major
areas:

• Analysis of individual steps of phosphoinositide metabolism in a model system for hippocampal neurons by a combination of experimental and computational approaches. Development of mathematical models of phosphoinositide-dependent processes such as action potential firing of hippocampal neurons in response to simulated stimulation by neurotransmitters.
• Analysis of second messenger signaling downstream of PI(4,5)P₂ hydrolysis, specifically mediation of intracellular Ca²⁺-signaling by IP₃ receptor-binding protein released with inositol 1,4,5-trisphosphate.

Publications

1. Jensen J, Falkenburger BH, Dickson EJ, de la Cruz L, Dai G, Myeong J, Jung SR, Kruse M, Vivas O, Suh BC, and Hille B (2022). Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells. J Gen Physiol 154(6): e:202113074.

2. de la Cruz L, Kushmerick C, Sullivan JM, Kruse M*, and Vivas O* (2022). Hippocampal neurons maintain a large PtdIns(4)P pool that results in faster PtdIns(4,5)P2 synthesis. J Gen Physiol 154(3): e:202113001. * Oscar Vivas and Martin Kruse are shared senior authors of this publication.

3. Flenner F, Jungen C, Küpker N, Ibel A, Kruse M, Koivumäki JT, Rinas A, Zech ATL, Rhoden A, Wijnker PJM, Lemoine MD, Steenpass A, Girdauskas E, Eschenhagen T, Meyer C, van der Velden J, Patten-Hamel M, Christ T, and Carrier L (2021). Translational investigation of electrophysiology in hyperthrophic cardiomyopathy. J Mol Cell Cardiol 157: 77-89.

4. Kruse M, and Whitten RJ# (2021). Control of neuronal excitability by cell surface receptor density and phosphoinositide metabolism. Front Pharmacol 12: 663840. # Undergraduate student mentored by M. Kruse.

5. Chua GNL, Wassarman KL, Sun H, Alp JA, Jarczyk EI, Kuzio NJ, Bennett MJ, Malachowsky BG, Kruse M, and Kennedy AJ (2019). Cytosine-based TET enzyme inhibitors. ACS Med Chem Lett 10: 180-185.

6. Kruse M, Kohout SC, and Hille B (2019). Reinterpretation of the substrate specificity of the voltage- sensitive phosphatase during dimerization. J Gen Physiol 151: 258-263.

7. Walter AM, Mueller R, Tawfik B, Wierda KD, Pinheiro PS, Nadler A, McCarthy AW, Ziomkiewicz I, Kruse M, Reither G, Rettig J, Lehmann M, Haucke V, Hille B, Schultz C, and Sorensen JB (2017). Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis. eLIFE e30203.

8. Traynor-Kaplan A, Kruse M, Dickson EJ, Dai G, Vivas O, Yu H, Whittington D, and Hille B (2017). Fatty- acyl chain profiles of cellular phosphoinositides. Biochim Biophys Acta – Molecular and Cell Biology of Lipids 1862: 513-522.

9. Dai G, Yu H, Kruse M, Traynor-Kaplan A, and Hille B (2016). Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels. Proc Natl Acad Sci USA 113: E3290- 9.

10. Keum D*, Kruse M*, Kim DI, Hille B, and Suh BC (2016). Phosphoinositide 5- and 3- phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence. Proc Natl Acad Sci USA 113: E3686-95. * These authors contributed equally to this work

11. Yu H, Benitez SG, Jung SR, Altamirano LE, Kruse M, Seo JB, Koh DS, Muñoz EM, and Hille B (2016). GABAergic signaling in the rat pineal gland. J Pineal Res 61: 69-81.

12. Dickson EJ, Jensen JB, Vivas O, Kruse M, Traynor-Kaplan A, and Hille B (2016). Rapid formation of ER-PM junctions recruits a lipid phosphatase and regulates phosphoinositide metabolism. JCB 213: 33-48.

13. Kruse M*, Vivas O*, Traynor-Kaplan A, and Hille B (2016). Dynamics of phosphoinositide-dependent signaling in sympathetic neurons. J Neurosci 36: 1386-400. * These authors contributed equally to this work. (Recommended in Faculty of 1000)

14. Hille B, Dickson EJ, Kruse M, Vivas O, Suh BC (2015). Phosphoinositides regulate ion channels. Biochim Biophys Acta 1851: 844-56.

15. Vivas O*, Kruse M*, Hille B (2014). Nerve growth factor sensitizes adult sympathetic neurons to the proinflammatory peptide bradykinin. J Neurosci 34: 11959-71. * These authors contributed equally to this work.

16. Kruse M, Pongs O (2014). TRPM4 channels in the cardiovascular system. Curr Opin Pharmacol 15: 68-73.

17. Hille B, Dickson E, Kruse M, Falkenburger B (2014). Dynamic metabolic control of an ion channel. Prog Mol Biol Transl Sci 123: 219-47.

18. Kruse M, Hille B (2013). The phosphoinositide sensitivity of the KV channel family. Channels 7: 530- 6.

19. Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Brück W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA (2012). TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 18: 1805-11. (Recommended in Faculty of 1000)

20. Mandal G, Sharma M, Kruse M, Sander-Juelch C, Munro LA, Wang Y, Vilg JV, Tamás MJ, Bhattacharjee H, Wiese M, Mukhopadhyay R (2012). Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase. Mol Microbiol 85: 1204-18.

21. Kruse M, Hammond GR, Hille B (2012). Regulation of voltage-gated potassium channels by PI(4,5)P2. J Gen Physiol 140: 189-205.

22. Klaiber M*, Dankworth B*, Kruse M*, Hartmann M, Nikolaev VO, Yang RB, Völker K, Gassner B, Oberwinkler H, Feil R, Freichel M, Groschner K, Skryabin BV, Frantz S, Birnbaumer L, Pongs O, Kuhn M (2011). A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide. Proc Natl Acad Sci USA 108: 18500-5. * These authors contributed equally to this work.

23. Sachse G, Kruse M, Pongs O (2011). Genetically Modified Mice: Useful Models to Study Cause and Effect of Cardiac Arrhythmias? Heart Rate and Rhythm, 473-84.

24. Klaiber M, Kruse M, Völker K, Schröter J, Feil R, Freichel M, Baba HA, Pongs O, Penninger JM, and Kuhn M (2010). Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. Basic Res Cardiol 105: 583-95. (Recommended in Faculty of 1000)

25. Liu H*, El Zein L*, Kruse M*, Guinamard R, Beckmann A, Bozio A, Kurtbay G#, Mégarbané A, Ohmert I, Blaysat G, Vilain E, Pongs O, and Bouvagnet P (2009). Gain- of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease. Circ Cardiovasc Genet 3: 374-85. * These authors contributed equally to this work. # Undergraduate student mentored by M. Kruse.

26. Kruse M*, Schulze-Bahr E*, Corfield V*, Beckmann A, Stallmeyer B, Kurtbay G#, Ohmert I, Schulze- Bahr El, Brink P, and Pongs O (2009). Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. JCI 119: 2737-44. * These authors contributed equally to this work. # Undergraduate student mentored by M. Kruse. (Recommended in Faculty of 1000)

27. Wang Q, Melzer IM, Kruse M, Sander-Juelch C, and Wiese M (2005). LmxMPK4, a mitogen- activated protein (MAP) kinase homologue essential for promastigotes and amastigotes of Leishmania mexicana. Kinetoplastid Biol Dis 4: 6.

28. Cross FR, Schroeder L, Kruse M, and Chen KC (2005). Quantitative characterization of a mitotic cyclin threshold regulating exit from mitosis. Mol Biol Cell 16: 2129-38.

Education

BS & BA                                University of Rochester (2001)

Liberal Arts Diploma      European College of Liberal Arts (ECLA) (2002)

PhD                                        University of Pittsburgh (2008)

Research Interests

Professor Castro studies the sense of smell, focusing on 1) understanding the neural circuitry involved in odor processing, and 2) elucidating systematic relationships between chemical structures and odor percepts.

 1. Neural circuitry of odor processing: 

The olfactory system can detect and discriminate between a huge number of chemical stimuli. How does it do it, and what aspects of neural function facilitate these operations? To address these questions, Professor Castro studies the properties of circuits in the olfactory bulb – the first brain structure of the odor processing stream. Using electrical recording and imaging techniques, Prof. Castro studies how the intrinsic and synaptic properties of neurons contribute to their ability to sensitively and selectively respond to inputs. Current work is focusing on the heterogeneity of neural properties in the olfactory bulb to study whether it functions as a collection of ‘generalists’, or independent ‘specialists.’

 2. Structure-Percept mapping:

One of the major challenges in olfactory research is to determine whether there is a systematic relationship between physiochemical features of molecules and their perceived smell. Despite a rich tradition of studying this question, it is still extremely difficult to predict odor qualities (like ‘woody’, ‘chemical’, or ‘fruity’) from knowledge of chemical structure alone.  In collaboration with investigators at the University of Pittsburgh and Oak Ridge National Laboratories, Professor Castro is applying data-mining and dimensionality reduction techniques to large chemical and perceptual databases to derive principles for predicting odor quality from chemical structure. Future work will test these principles in experiments with human subjects.

Courses Taught

• NRSC/PSYC 160 Introduction to Neuroscience
• DCS/NRSC/PSYC 357 Computational Neuroscience
• NRSC/PSYC 363 Physiological Psychology
• NRSC/PSYC 364 Psychobiology of Smell
• PSYC 305 Animal Learning
• NRSC 462 Capstone Seminar on Computational Neuroscience

Selected Publications

 Castro JB, Ramanathan A, and Chennubhotla C.  Analysis of odor perceptual space using non-negative matrix factorization (submitted).

Castro JB, and Urban N. Tuft calcium spikes in mitral cells evoke glutamate release (submitted).

Castro JB, Kandler K. Changing tune in auditory cortex (2010). Nat Neurosci.  13(3):271-3

Castro JB, Urban NN. Subthreshold glutamate release from mitral cell dendrites (2009).  J Neurosci. 29(21):7023-30.

Castro JB, Hovis KR, Urban NN. Recurrent dendrodendritic inhibition of accessory olfactory bulb mitral cells requires activation of group I metabotropic glutamate receptors (2007). J Neurosci.  27(21):5664-71.

Urban NN, Castro JB. Tuft calcium spikes in accessory olfactory bulb mitral cells (2005). J Neurosci. 25(20):5024-8.