Program of Biophysics · University of Michigan

Magdalena Ivanova, PhD

Protein folding, phase separation, and aggregation in neurodegenerative disease.

Affiliations in the Neuroscience Graduate Program and the Michigan Neuroscience Institute.

About

Our research examines protein folding, liquid–liquid phase separation, and aggregation, and how these processes contribute to disease. We study the misfolding, toxic species formation, and abnormal assembly of proteins including α-synuclein, amyloid-β, tau, TDP-43, and UBQLN2, whose pathogenic accumulation underlies a group of devastating and often terminal disorders known as proteinopathies. Combining biophysics, computational modeling, biochemistry, and cell biology, we work to define the mechanisms driving protein misfolding and to translate that understanding into therapeutic strategies.

Research

Two questions at the center of our work.

Our projects connect molecular self-assembly with protein quality control, disease-specific structures, propagation, and cellular outcomes.

Brain-expressed ubiquilins in normal function and disease

The brain-expressed ubiquilins (UBQLN1, 2, and 4) maintain protein homeostasis by clearing damaged and misfolded proteins; mutations in UBQLN2 and UBQLN4 drive pathogenic aggregation in familial ALS/FTD, and ubiquilin dysfunction has been linked to Huntington's disease and the synucleinopathies. Liquid–liquid phase separation appears central to how they work — concentrating them where needed, but also tipping them toward pathological aggregation. We ask what governs that balance at the molecular level, in health and in disease.

ProteostasisPhase separationALS / FTD

Molecular studies of α-synuclein aggregation

One protein, several diseases. α-Synuclein aggregates in Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease with Lewy bodies, and multiple system atrophy — yet these disorders differ markedly in pathology and clinical course. We think the answer lies in structure: using computational, biophysical, and cellular approaches, we characterize the structural heterogeneity of α-synuclein inclusions across these diseases and ask how distinct assemblies give rise to distinct phenotypes and how they propagate.

Structural heterogeneityPropagationSynucleinopathies

Teaching

Physics and chemistry as tools for understanding life.

Courses connect foundational principles with biological systems, biomedical applications, quantitative analysis, landmark discoveries, and modern biophysical tools.

Fall 2026

Biophysics of Life

BIOPHYS 120

Fall 2026

Physical & Chemical Principles Behind Biology and Medicine

BIOPHYS 370 · CHEM 370

Winter 2026

Biocomplexity

BIOPHYS 433 · PHYSICS 433

Winter 2026

Medical Physics

BIOPHYS 430 · PHYSICS 430

Teaching history

Biophysics of Life / Discovery of the DNA Double Helix — since Fall 2025
Physical and Chemical Principles Behind Biology and Medicine — since Fall 2024
Medical Physics — since Winter 2020
Biocomplexity — since Winter 2025
Biophysics of Disease — Fall 2014–Fall 2024

Course listings are available through the Biophysics undergraduate courses page. Interested students are welcome to get in touch.

Editorial & Service

Journal

Editor, Biophysical Chemistry

Serving on the editorial board of Elsevier's Biophysical Chemistry, handling manuscripts across protein biophysics and proteinopathies.

Editorial board Society

Chair, Communication Committee — ISP

Chairing the Communication Committee of the International Society for Proteinopathies (ISP), coordinating outreach across the community.

Committees

Book project

Biomedical Physics with Applications to Disease

Writing a book on biomedical physics, computation, and AI for understanding disease.

Explore the book Book app

Publications

Recent work, 2020–2026.

Browse peer-reviewed research spanning amyloid oligomers, membrane interactions, ubiquilins, α-synuclein, C9orf72, NOTCH3, and protein quality control.

Google Scholar PubMed / NCBI

Selected · since 2020

Ivanova MI*, La Rosa C*, Ramamoorthy A* 2026. Toxic mechanisms of amyloid oligomers and therapeutic strategies. Protein Sci 35(4), e70519. *shared correspondence
Ivanova MI*, La Rosa C*, Ramamoorthy A* 2026. In vitro, cellular and in vivo studies of amyloid oligomers structure and toxicity: challenges and advances. Protein Sci 35(4), e70525. *shared correspondence
Desai AA, Smith MD, Zupancic JM, Makowski MK, Zhang Y, Gerson JE, Moore SJ, Sutter AB, Ferris SP, Ivanova MI, Murphy GG, Paulson HL, Tessier PM 2025. Directed evolution of drug-like Aβ conformation-specific antibodies. Front Immunol 16, 1655893.
Sharma G, Krishnarjuna B, Hiiuk VH, Ivanova MI, Nagorny P, Ramamoorthy A 2025. Detergent-free isolation and characterization of amyloid precursor protein C99 in E. coli native lipid-nanodiscs using non-ionic polymer. Protein Sci 34(9), e70276.
McCalpin SD, Mechakra L, Ivanova MI*, Ramamoorthy A* 2024. Differential effects of ganglioside lipids on the conformation and aggregation of islet amyloid polypeptide. Protein Sci 33(8), e5119. *shared correspondence
McCalpin SD, Khemtemourian L, Suladze S, Ivanova MI, Reif B, Ramamoorthy A 2024. Zinc and pH modulate the ability of insulin to inhibit aggregation of islet amyloid polypeptide. Commun Biol 7(1), 776.
Krishnarjuna B, Sharma G, Hiiuk VM, Struppe J, Nagorny P, Ivanova MI, Ramamoorthy A 2024. Nanodisc reconstitution and characterization of amyloid-β precursor protein C99. Anal Chem 96(23), 9362–9369.
Kumar M, Ivanova MI, Ramamoorthy A 2023. Non-micellar ganglioside GM1 induces an instantaneous conformational change in Aβ42 leading to modulation of the peptide amyloid-fibril pathway. Biophys Chem 301, 107091.
Peelaerts W, Mercado G, George S, Villumsen M, Kasen A, Aguileta M, et al., Ivanova MI, Hannan TJ, Brundin P 2023. Urinary tract infections trigger synucleinopathy via the innate immune response. Acta Neuropathol 145(5), 541–559.
Wu SA, Shen C, Wei X, Zhang X, Wang S, Chen X, et al., Ivanova MI, Lin Y, Qi L 2023. The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes. Nat Commun 14(1), 3132.
Kumar M, Ivanova MI, Ramamoorthy A 2023. Ganglioside GM1 produces stable, short, and cytotoxic Aβ40 protofibrils. Chem Commun (Camb) 59(46), 7040–7043.
Shahpasand-Kroner H, Siddique I, Malik R, Linares GR, Ivanova MI, Ichida J, et al., Bitan G 2022. Molecular tweezers: supramolecular hosts with broad-spectrum biological applications. Pharmacol Rev 75(2), 263–308.
Sahoo BR, Souders CL 2nd, Watanabe-Nakayama T, Deng Z, Linton H, Suladze S, Ivanova MI, Reif B, Ando T, Martyniuk CJ, Ramamoorthy A 2022. Conformational tuning of amylin by charged styrene-maleic-acid copolymers. J Mol Biol 434, 167385.
Wright SE, Rodriguez CM, Monroe J, Xing J, Krans A, Flores BN, Barsur V, Ivanova MI, Koutmou KS, Barmada SJ, Todd PK 2022. CGG repeats trigger translational frameshifts to generate aggregation-prone chimeric proteins. Nucleic Acids Res 50(15), 8674–8689.
Young KZ, Rojas Ramírez C, Keep SG, Gatti JR, Lee SJ, Zhang X, Ivanova MI, Ruotolo BT, Wang MM 2022. Oligomerization, trans-reduction, and instability of mutant NOTCH3 in inherited vascular dementia. Commun Biol 5(1), 331.
Krishnarjuna B, Ivanova MI, Ramamoorthy A 2021. Aggregation and the intrinsic structural disorder of dipeptide repeat peptides of C9orf72-related ALS and FTD characterized by NMR. J Phys Chem B 125, 12446–12456.
Young KZ, Cartee NMP, Lee SJ, Keep SG, Ivanova MI, Wang MM 2021. Electrophilic and drug-induced stimulation of NOTCH3 N-terminal fragment oligomerization in cerebrovascular pathology. Transl Stroke Res, 1–12.
Gerson JE, Linton H, Xing J, Sutter AB, Kakos FS, Ryou J, Liggans N, Sharkey LM, Safren N, Paulson HL, Ivanova MI 2021. Shared and divergent phase separation and aggregation properties of brain-expressed ubiquilins. Sci Rep 11(1), 1–13.
Desai AA, Smith MD, Zhang Y, Makowski EK, Gerson JE, Ionescu E, Starr CG, Zupancic JM, Moore SJ, Sutter AB, Ivanova MI, Murphy GG, Paulson HL, Tessier PM 2021. Rational affinity maturation of anti-amyloid antibodies with high conformational and sequence specificity. J Biol Chem, 100508.
Cox SJ, Rodriguez Camargo DC, Lee YH, Dubini RCA, Rovó P, Ivanova MI, Padmini V, Reif B, Ramamoorthy A 2020. Small molecule induced toxic human-IAPP species characterized by NMR. Chem Commun (Camb) 56(86), 13129–13132.
Cox SJ, Lam B, Prasad A, Marietta HA, Stander NV, Joel JG, Sahoo BR, Guo F, Stoddard AK, Ivanova MI, Ramamoorthy A 2020. High-throughput screening at the membrane interface reveals inhibitors of amyloid-β. Biochemistry 59(24), 2249–2258.
Ivanova MI, Lin Y, Lee YH, Zheng J, Ramamoorthy A 2020. Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology. Biophys Chem 269, 106507.
Young KZ, Cartee NMP, Ivanova MI, Wang MM 2020. Thiol-mediated and catecholamine-enhanced multimerization of a cerebrovascular disease enriched fragment of NOTCH3. Exp Neurol 328, 113261.
Lempart J, Tse E, Lauer JA, Ivanova MI, Sutter A, Yoo N, Huettemann P, Southworth D, Jakob U 2019. Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity. Life Sci Alliance 2(5), e201900486.
Green KM, Sheth UJ, Flores BN, Wright SE, Sutter AB, Kearse MG, Barmada SJ, Ivanova MI, Todd PK 2019. High-throughput screening yields several small-molecule inhibitors of repeat-associated non-AUG translation. J Biol Chem 294(49), 18624–18638.
Lee YH, Lin Y, Cox SJ, Kinoshita M, Sahoo BR, Ivanova M, Ramamoorthy A 2018. Zinc boosts EGCG’s hIAPP amyloid inhibition both in solution and membrane. Biochim Biophys Acta Proteins Proteom 1867(5), 529–536.
Hanczyc P, Justyniarski A, Kim J, Mikhalovsky A, Ivanova M 2018. Surface patterns of insulin fibrils revealed by time-resolved spectroscopy measurements of fluorescent probes. J Lumin 201, 31–37.
Sharkey LM, Safren N, Pithadia AS, Gerson JE, Dulchavsky M, Fischer S, Patel R, Lantis G, Ashraf N, Kim JH, Meliki A, Minakawa EN, Barmada SJ, Ivanova MI*, Paulson HL* 2018. Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly. Proc Natl Acad Sci USA 115(44), E10495–E10504. *shared co-corresponding
Sahoo BR, Genjo T, Bekier M, Cox SJ, Stoddard AK, Ivanova M, Yasuhara K, Fierke CA, Wang Y, Ramamoorthy A 2018. Alzheimer’s amyloid-β intermediates generated using polymer-nanodiscs. Chem Commun (Camb) 54(91), 12883–12886.
Vega IE, Sutter A, Parks L, Umstead A, Ivanova MI 2018. Tau’s three-repeat domain and EFhd2 coincubation leads to increased thioflavin signal. Front Neurosci 12, 879.
Korshavn KJ, Satriano C, Lin Y, Zhang R, Dulchavsky M, Bhunia A, Ivanova MI, Lee YH, La Rosa C, Lim MH, Ramamoorthy A 2017. Reduced lipid bilayer thickness regulates the aggregation and cytotoxicity of amyloid-β. J Biol Chem 292(11), 4638–4650.
Jain N, Ådén J, Nagamatsu K, Evans ML, Li X, McMichael B, Ivanova MI, Almqvist F, Buxbaum JN, Chapman MR 2017. Inhibition of curli assembly and Escherichia coli biofilm formation by the human systemic amyloid precursor transthyretin. Proc Natl Acad Sci USA 114(46), 12184–12189.
Popp D, Loh ND, Zorgati H, Ghoshdastider U, Liow LT, Ivanova MI, et al. 2017. Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free electron laser. Cytoskeleton (Hoboken) 74(12), 472–481.
Costa MDC, Ashraf NS, Fischer S, Yang Y, Schapka E, Joshi G, McQuade TJ, Dharia RM, Dulchavsky M, Ouyang M, Cook D, Sun D, Larsen MJ, Gestwicki JE, Todi SV, Ivanova MI, Paulson HL 2016. Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3. Brain 139(11), 2891–2908.
Lulla A, Barnhill L, Bitan G, Ivanova MI, Nguyen B, O’Donnell K, Stahl MC, Yamashiro C, Klärner FG, Schrader T, Sagasti A, Bronstein JM 2016. Neurotoxicity of the Parkinson disease-associated pesticide ziram is synuclein-dependent in zebrafish embryos. Environ Health Perspect 124(11), 1766–1775.
Flores BN, Dulchavsky ME, Krans A, Sawaya MR, Paulson HL, Todd PK, Barmada SJ, Ivanova MI 2016. Distinct C9orf72-associated dipeptide repeat structures correlate with neuronal toxicity. PLoS One 11(10), e0165084.
Rodriguez JA*, Ivanova MI*, Sawaya MR*, Cascio D, Reyes FE, Shi D, Sangwan S, Guenther EL, Johnson LM, Zhang M, Jiang L, Arbing MA, Nannenga BL, Hattne J, Whitelegge J, Brewster AS, Messerschmidt M, Boutet S, Sauter NK, Gonen T, Eisenberg DS 2015. Structure of the toxic core of α-synuclein from invisible crystals. Nature 525(7570), 486–490. *shared co-first author
Li D, Jones EM, Sawaya MR, Furukawa H, Luo F, Ivanova M, Sievers SA, Wang W, Yaghi OM, Liu C, Eisenberg DS 2015. Structure-based design of functional amyloid materials. J Am Chem Soc 136(52), 18044–18051.
Acharya S, Safaie BM, Wongkongkathep P, Ivanova MI, Attar A, Klärner FG, Schrader T, Loo JA, Bitan G, Lapidus LJ 2014. Molecular basis for preventing α-synuclein aggregation by a molecular tweezer. J Biol Chem 289(15), 10727–10737.
Ivanova MI, Sievers SA, Guenther EL, Johnson LM, Winkler DD, Galaleldeen A, Sawaya MR, Hart PJ, Eisenberg DS 2014. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS. Proc Natl Acad Sci USA 111(1), 197–201.
Whidden M, Ho A, Ivanova MI, Schnell S 2014. Competitive inhibition reaction mechanisms for the two-step model of protein aggregation. Biophys Chem 193–194, 9–19.
Weiss WF 4th, Zhang A, Ivanova MI, Sahin E, Jordan JL, Fernandez EJ, Roberts CJ 2014. Reduction of the C191–C220 disulfide of α-chymotrypsinogen A reduces nucleation barriers for aggregation. Biophys Chem 185, 79–87.
Prabhudesai S, Sinha S, Attar A, Kotagiri A, Fitzmaurice AG, Lakshmanan R, Ivanova MI, Loo JA, Klärner FG, Schrader T, Stahl M, Bitan G, Bronstein JM 2012. A novel “molecular tweezer” inhibitor of α-synuclein neurotoxicity in vitro and in vivo. Neurotherapeutics 9(2), 464–476.
Zhang A, Jordan JL, Ivanova MI, Weiss WF 4th, Roberts CJ, Fernandez EJ 2010. Molecular level insights into thermally induced α-chymotrypsinogen A amyloid aggregation mechanism and semiflexible protofibril morphology. Biochemistry 49(49), 10553–10564.
Ivanova MI, Sievers SA, Sawaya MR, Wall JS, Eisenberg D 2009. Molecular basis for insulin fibril assembly. Proc Natl Acad Sci USA 106(45), 18990–18995.
Sawaya MR*, Sambashivan S*, Nelson R*, Ivanova MI*, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJ, McFarlane HT, Madsen AØ, Riekel C, Eisenberg D 2007. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447(7143), 453–457. *shared co-first author
Eisenberg D, Nelson R, Sawaya MR, Balbirnie M, Sambashivan S, Ivanova MI, Madsen AØ, Riekel C 2006. The structural biology of protein aggregation diseases: fundamental questions and some answers. Acc Chem Res 39(9), 568–575.
Ivanova MI, Thompson MJ, Eisenberg D 2006. A systematic screen of β2-microglobulin and insulin for amyloid-like segments. Proc Natl Acad Sci USA 103(11), 4079–4082.
Thompson MJ, Sievers SA, Karanicolas J, Ivanova MI, Baker D, Eisenberg D 2006. The 3D profile method for identifying fibril-forming segments of proteins. Proc Natl Acad Sci USA 103(11), 4074–4078.
Ivanova MI, Sawaya MR, Gingery M, Attinger A, Eisenberg D 2004. An amyloid-forming segment of β2-microglobulin suggests a molecular model for the fibril. Proc Natl Acad Sci USA 101(29), 10584–10589.
Ivanova MI, Gingery M, Whitson LJ, Eisenberg D 2003. Role of the C-terminal 28 residues of β2-microglobulin in amyloid fibril formation. Biochemistry 42(46), 13536–13540.
Ivanova MI, Makowski L 1998. Iterative low pass filtering of the background in fiber diffraction patterns. Acta Crystallogr A 54, 626–631.

Scholarly record

7,137Citations

29h-index

39i10-index

Citation metrics via Google Scholar · Updated August 2026.

Contact

Magdalena I. Ivanova, PhD Program of Biophysics
930 N. University Ave.
University of Michigan
Ann Arbor, MI 48109
Phone 734 647 9869
Email [email protected]

Elsewhere

Google Scholar PubMed Biophysical Chemistry ISP Committees