Translating Proteomics

Unlike “globular” proteins that adopt stable structures that are relatively easy to analyze, intrinsically disordered proteins adopt many context-dependent shapes. These shapes may drive diverse functions, but they are also difficult to capture and study. This represents a large gap in our understanding of biology, given that most proteins may have intrinsically disordered regions. Thankfully, researchers like Professor Priyanka Joshi, Ph.D., from Georgetown University have devoted themselves to studying intrinsically disordered proteins and are developing new approaches and leveraging new technologies like the Nautilus Voyager™ Platform to discover how their dynamic structures influence biological function. Because intrinsically disordered proteins often aggregate in disease, this work is not only essential to our understanding of biology but may also enable the development of effective biomarkers and treatments for diseases like Alzheimer’s.

Parag interviews Professor Joshi on this episode of Translating Proteomics to discover:

• What intrinsically disordered proteins are
• How intrinsically disordered proteins influence biology and why they’re hard to study
• How the recently announced SEEDS Consortium is studying intrinsically disordered proteins

00:00 – Introduction to Prof. Priyanka Joshi, Ph.D.

04:35 – What are intrinsically disordered proteins (IDPs)?

11:41 – When do intrinsically disordered proteins go bad in disease?

23:02 – Archetypal Intrinsically disordered proteins – c-Myc/Max, p53, and Tau

38:26 – Barriers to solving the problems associated with intrinsically disordered proteins

43:30 – The future of intrinsically disordered protein research and introducing the SEEDS Consortium

https://pubmed.ncbi.nlm.nih.gov/26923286/

Joshi, Priyanka et al. “A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.” ACS combinatorial science vol. 18,3 (2016): 144-53. doi:10.1021/acscombsci.5b00129

Priyanka’s 2016 work developing small-molecule libraries to target IDPs

https://www.georgetown.edu/news/georgetown-and-buck-institute-awarded-up-to-51-7m-to-predict-protein-changes-linked-to-alzheimers-and-some-cancers/

Georgetown University press release covering the SEEDS Consortium

https://investors.nautilus.bio/news-releases/news-release-details/nautilus-measure-proteoforms-driving-alzheimers-disease-and

Nautilus Biotechnology press release covering its involvement in the SEEDS Consortium

Professor Brendan Keating’s lab focuses on “advancing the field of organ transplantation” and employs multiomic techniques to improve outcomes for both allo- (human to human) and xeno- (animal to human) transplantation. He’s using multiomics to better understand the mechanisms of rejection and acceptance with a particular focus on immunologic barriers in cross-species transplantation. Professor Keating joins Translating Proteomics to discuss:

• The current state of transplant medicine including xenotransplantation
• How multiomics is changing transplant medicine
• The future of transplant medicine.

00:00 – Introduction

05:00 - Transplantation Today: Outcomes, Challenges, and the Organ Shortage

10:06 - From Genetics to Multiomics

19:53 - Xenotransplantation deep dive

30:42 - Ten‑Year Vision: Transplants and the Role of Multiomics

Translating Proteomics hosts Parag Mallick and Andreas Huhmer discuss our new Nature Methods paper, “Large-scale single-molecule analysis of tau proteoforms.” This publication describes how the Nautilus Voyager™ Platform can be used to quantify proteoforms derived from the neurodegeneration-associated tau protein. These proteoforms are defined by their unique combinations of post-translational modifications and isoform specific sequences. They may make powerful next-generation biomarkers or drug targets, but few technologies can measure them today.

In the episode, Parag and Andreas discuss:

• What proteoforms are and why it’s critical to study them to understand biology.
• How the Nautilus Voyager™ Platform quantifies proteoforms.
• The key findings from the tau proteoform analyses in the paper.
• Potential applications of these findings.
• The Nautilus Voyager™ Platform as a powerful foundational technology.

Access our video series exploring the paper in more detail.

On the latest episode of the Translating Proteomics podcast, Nautilus VP of Scientific Engagement and proteomics industry expert Sheri Wilcox joins hosts Parag Mallick and Andreas Huhmer for a thought-provoking discussion of their proteomics "hot takes.”

Each “hot take” is a provocative opinion on a topic in proteomics. Specifically, they cover:

• Insufficient biological validation is one of the biggest problems in proteomics.
• Antibody validation remains a distributed, inconsistent, lab-by-lab responsibility, and this model for validation may not be sustainable going forward.
• AI cell models are overhyped.

Check out the episode for deep explorations of each of these hot takes and their potential remedies.

After listening, be sure to let us know whether you agree, disagree, or have your own hot take to share!

Professor Olga Vitek has a deep understanding of statistics, machine learning, and computational biology. She puts her know-how to work to develop computational tools enabling high-quality proteomic analysis and systems biology approaches. She hopes to apply these tools to the quantitative analysis of large-scale mass spectrometry-based investigations and thereby advance our understanding of organismal function. In this episode, Parag and Professor Vitek discuss:

1. Why statistics is important for experimental design
2. How statistics and AI can help researchers understand biology
3. Gaps keeping us from using AI and statistics to their maximum potential in biology

Statistical methods for studies of biomolecular systems website

1. Olga’s personal lab website

Beyond protein lists: AI-assisted interpretation of proteomic investigations in the context of evolving scientific knowledge

1. Gyori and Vitek, 2024 discuss how AI can be used to interpret proteomics data and its biological meaning.

A Bayesian Active Learning Experimental Design for Inferring Signaling Networks

1. Ness et al., 2018 show how statistical methods can guide the selection of experiments that optimally enhance understanding

Host Parag Mallick chats with Professor Afshin Beheshti who is a Professor of Surgery, Director of the Center for Space Biomedicine, and Associate Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. In addition, Professor Beheshti has a visiting researcher appointment at the Broad Institute of MIT and Harvard and is president of two non-profits – the COVID-19 International Research Team and Kwaai. The latter aims to democratize access to artificial intelligence through the design, construction, and maintenance of a free personal AI called Kwaai.

Professor Beheshti’s research covers a range of topics focused on how circulating mirco RNAs and mitochondria impact health, but this conversation focuses primarily on Professor Beheshti’s work advancing our understanding of how spaceflight impacts biology. We cover:

1. How research on spaceflight and biology is done
2. Gaps that remain in our understanding of spaceflight and biology
3. Omics studies of spaceflight and biology
4. How studying spaceflight and biology enhances our understanding of human health more broadly

Trivedi Institute for Space and Global Biomedicine

1. New Institute at the University of Pittsburgh focused on “advancing human health through space-driven innovation”

NASA Open Science Data Repository

1. "Provides open access to biological and physical science datasets from spaceflight and ground studies, enabling data reuse for discovery and innovation."

Camera et al., 2024. Agining and putative frailty biomarkers are altered by spaceflight

1. Study on molecular biomarkers and frailty phenotypes in space

Overbey et al., 2024. The Space Omics and Medical Atlas (SOMA) and international astronaut biobank

1. An “integrated data and sample repository for clinical, cellular, and multi-omic research profiles” from a variety of space missions
2. Space Omics and Medical Atlas (SOMA) website

Corti et al., 2024. To boldly go where no microRNAs have gone before: spaceflight impact on risk for small-for-gestational-age infants

1. Explores how miRNA signatures of “small-for-gestational-age” are impacted by the space environment

Beheshti et al., 2013. Age and space irradiation modulate tumor progression: implications for carcinogenesis risk

1. Some of Professor Beheshti’s early work studying connections between spaceflight and cancer progression.

Kwaai

1. Nonprofit "building a no-cost open source Personal AI assistant"

On this episode of Translating Proteomics, Parag and Andreas share their reflections on proteomics developments in 2025 largely inspired by their observations at the World HUPO 2025 conference in Toronto. Whether you agree, disagree, or simply want to share some of your own observations on proteomics, please post your thoughts in the comments.

We look forward to even more exciting developments in 2026!

00:00 - 00:35 – Intro

00:36 – 07:00 - Increased focus on applications of proteomics and less on method development

Learn more about One Health from our conversation with Professor Jennifer Geddes-McAlister

https://youtu.be/JFwvTdkb5bw

07:01 – 12:47 - Increase in people talking about the importance of proteoforms

Learn more about proteoforms in our episode featuring proteoform pioneer Professor Neil Kelleher

https://youtu.be/3pPuxVrMxpw

12:47 – 17:26 - An increase in multiomics studies

17:27 – 20:03 - A shift to larger scale proteomics studies

For a great example of a multi-platform comparison study, check out Kirsher et al., 2025

https://www.nature.com/articles/s42004-025-01665-1

20:03 – 25:07 - Increased integration of AI into proteomics workflows

For an example of how proteomics workflows can be modified with multiomic data, check out Suhre et al., 2025

https://www.nature.com/articles/s41588-025-02413-w

25:08 – 30:05 – Recognition of the need to assess quality across proteomics workflows

30:06 – 32:19 – Less of a focus on spatial proteomics this year than in past years

32:20 – 35: 13 - Parag and Andreas share their predictions for 2026

35:14 – End – Outro

On this episode of Translating Proteomics, Parag speaks with Professor Jennifer Geddes-McAlister from the University of Guelph. Professor Geddes-McAlister is an expert at using proteomics to study host-microbe interactions from a systems biology perspective. Her exciting work spans studies of pathogenic fungi all the way to engineering plants to produce pharmaceutics (so-called “molecular pharming"). On top of all that, Professor Geddes-McAlister also founded “Moms in Proteomics” to support and encourage an intentional focus on the inherently unique physical, emotional, and biological commitments of Mothers, and the ensuing balance required to excel within the diverse STEM fields encompassing Mass-Spectrometry-based proteomics.

Dive into this episode to:

• Learn why it’s critical to study hosts, pathogens, and molecular pharming from a systems point of view
• Discover what Professor Geddes-McAlister is excited about for the upcoming Human Proteome Organization (HUPO) conference
• Find out what “Moms in Proteomics” has planned for HUPO

00:00 - Intro

01:39 - Professor Geddes-McAlister's initial interest in host-microbe interactions

06:13 - Why it's important to study host-microbe interactions

08:10 - Pathogens vs helpful microbes

10:06 - Thinking about microbes through the lens of "One Health"

14:34 - Why Professor Geddes-McAlister works primarily in proteomics as opposed to other omes

19:44 - Professor Geddes-McAlister's favorite thing that she's learned from the proteome and couldn't learn from the other omes

24:56 - Molecular pharming

29:35 - The need for accessibility in proteomics

34:09 - The need for all-in-one workflows in proteomics

36:08 - HUPO 2025

39:56 - Moms in Proteomics

42:36 - The future of proteomics

43:59 - Outro

Geddes et al., 2015. Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A

https://pubmed.ncbi.nlm.nih.gov/26453029/

Some of Professor Geddes-McAlister’s early work using proteomics to study pathogenic fungi

Prudhomme et al., 2024. Bacterial growth-mediated systems remodelling of Nicotiana benthamiana defines unique signatures of target protein production in molecular pharming

https://onlinelibrary.wiley.com/doi/10.1111/pbi.14342

Researchers from Professor Geddes-McAlister’s lab use multiomic techniques to discover factors impacting the production of a pharmaceutical in an engineered plant

Woods et al., 2023. A One Health approach to overcoming fungal disease and antifungal resistance

https://wires.onlinelibrary.wiley.com/doi/full/10.1002/wsbm.1610

Review on the importance of incorporating “One Health” principals into efforts to fight pathogenic fungi

Moms in Proteomics website

https://momsinproteomics.ca

Learn all about the Moms in Proteomics initiative and its international community

On this episode of Translating Proteomics, Parag, Andreas, and special guest Don Kirkpatrick answer questions submitted by the Translating Proteomics community. They cover:

• Needs in plasma proteomics
• How proteomics impacts drug development – with special guest Don Kirkpatrick, Ph.D.!
• How lifestyle impacts the proteome
• How the Nautilus Proteome Analysis Platform is impacting tau and Alzheimer’s disease research

Shome et al., 2022 - Serum autoantibodyome reveals that healthy individuals share common autoantibodies

https://www.sciencedirect.com/science/article/pii/S2211124722006489

LaBaer Lab paper investigating autoantibody levels in plasma and their relationship to health.

Sylman et al., 2018 - A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patients

https://www.nature.com/articles/s41598-018-25019-1

Mallick lab paper investigating temporal changes in platelets and their associations with cancer biology.

Krönke et al., 2014 - Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells

https://www.science.org/doi/10.1126/science.1244851

Seminal paper describing selective protein degradation caused by lenalidomide.

Fink and Ebert 2015 - The novel mechanism of lenalidomide activity

https://ashpublications.org/blood/article/126/21/2366/34644/The-novel-mechanism-of-lenalidomide-activity

Review of research elucidating the mechanisms of lenalidomide activity

Ndoja et al., 2025 - COP1 Deficiency in BRAFV600E Melanomas Confers Resistance to Inhibitors of the MAPK Pathway

https://www.mdpi.com/2073-4409/14/13/975

Describe links between kinase inhibitor vemurafenib and changes in ETV transcription factor degradation

Song et al., 2022 - RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy

https://aacrjournals.org/cancerdiscovery/article/12/1/204/675622/RTK-Dependent-Inducible-Degradation-of-Mutant-PI3K

Use proteomics to discover that inavolisib acts through selective degradation of mutant PI3Kα

Canon et al., 2019 - The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

https://www.nature.com/articles/s41586-019-1694-1

Covers the development of an inhibitor of KRAS mutant KRAS (G12C).

Schneider et al., 2024 - Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axis

https://www.nature.com/articles/s42255-024-01108-6

Review on the gut-brain axis

Webpage for Johanna Lampe’s Lab at Fred Hutch Cancer Center

https://www.fredhutch.org/en/faculty-lab-directory/lampe-johanna.html

Guseh et al., 2020 - An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk

https://www.nature.com/articles/s41598-020-67669-0

Work investigating the relationship between exercise, the plasma proteome, and health

Human Proteome Organization (HUPO) webpage with resources focused on proteomics in space

https://hupo.org/Human-Proteomics-at-Extreme-Conditions

Joly et al., 2025 - Large-scale single-molecule analysis of tau proteoforms

https://doi.org/10.1101/2025.06.26.660445

Nautilus preprint using Iterative Mapping of proteoforms to measure tau proteoforms in Alzheimer’s disease and related dementias samples.

On this episode of Translating Proteomics, host Parag Mallick discusses spatial proteomics with special guest Fiona Ginty Ph.D. Fiona is a Senior Principal Scientist in Precision Diagnostics at the GE Healthcare Technology & Innovation Center. She is a leader in the development of spatial proteomics technologies and their application in precision diagnostics and medicine.

Their discussion covers:

·      How Fiona began working in spatial proteomics

·      Why spatial biology is important

·      What the future holds for spatial biology

00:00 – Introduction

01:54 – Fiona’s journey to biology

05:26 – Fiona’s transition to tool development

07:20 – Working at GE Research

11:26 – Identifying the importance of spatial biology

14:43 – How Cell DIVETM works

18:25 – The importance of single cell

23:01 - When Fiona realized the technology worked

28:04 – Spatial biology projects Fiona is excited about

30:08 – Fiona’s role in HuBMAP

36:50 – Learnings from HuBMAP so far

38:35 – The future of spatial proteomics in the clinic

46:56 – Current limits on spatial proteomics

49:56 – Current and future uses of AI in spatial proteomics

53:30 – The most exciting thing Fiona learned in her spatial proteomics journey

56:08 – Outro

Method of the Year 2024: Spatial Proteomics

Paper covering the spatial proteomics technology Fiona worked on at GE Healthcare

• Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue

HubMAP – Human BioMolecular Atlas Program

Human Tumor Atlas Network

Cell DIVE Multiplex Imaging Solution

Papers discussing what makes colorectal cancer cells undergo apoptosis in response to chemotherapy

• An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution
• Integrated multiplex analysis of cell death regulators in stage II colorectal cancer suggests patients with ‘persister’ cell profiles fail to benefit from adjuvant chemotherapy

Paper discussing how the distance between tumor cells and cytotoxic t-cells correlates to caspase level

• Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients - Azimi - 2024 - The Journal of Pathology - Wiley Online Library

Paper showing it takes 3 hits from cytotoxic t-cells to kill cancer cells

• Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity | Nature Communications

Paper focused on generating new pathology image patches using AI

• Predicting Breast Cancer Events in Ductal Carcinoma In Situ (DCIS) Using Generative Adversarial Network Augmented Deep Learning Model - PubMed

Dr. Ginty wanted to acknowledge the many people she’s worked with on Cell DIVE and as part of HuBMAP. She stresses that these are highly collaborative projects, and just some of the many great team members she's worked with are listed below.

Cell DIVE:

Anup Sood, Sean Dinn, Yunxia Sui, Sanghee Cho, John Graf , Kathleen Bove, Musodiq Bello, Sudeshna Adak, Michael Lazare, Anirban Bhaduri, Thomas Treynor, Dileep Vangasseri, Alberto Santamaria-Pang, Maureen Bresnahan, Micheal Gerdes, Megan Rothman, Colin McCullough, Chris Sevinsky, Liz McDonough, Christine Surrette, Max Seel, Alex Corwin, Bob Filkins, Kevin Kenny, Brion Sarachan, Mike Montalto, Christoph Hergersberg, John Burczak, Jens Rittscher, Steve Zingelewicz, Dr. Sunil Badve (Emory U), Dr. Yesim Gokmen Polar (Emory U), Eli Lilly collaborators

HuBMAP:

Lou Falo (U. Pitt), Arivarasan Karunamurthy (U. Pitt), John Hickey (Duke), Chenchen Zhu (Stanford), Ioannis Vlachos (BIDMC), Liz McDonough (GE HealthCare Technology and Innovation Center [HTIC]), Sammi Abate (GE HealthCare Technology and Innovation Center [HTIC]), Soumya Ghose (GE HealthCare Technology and Innovation Center [HTIC]), Christine Surrette (GE HealthCare Technology and Innovation Center [HTIC]), Dr. Katy Borner (Indiana U)