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High-Sensitive Spatial Proteomics for Pancreatic Cancer Progression Analysis

bioRxiv [Preprint]. 2025 May 5:2025.05.01.651678. doi: 10.1101/2025.05.01.651678.

ABSTRACT

Pancreatic cancer remains as one of the most challenging malignancies to diagnose and treat due to the late development of symptoms and limited early diagnostic options. Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursors to invasive pancreatic ductal adenocarcinoma (PDAC)and an understanding of the changes in patterns of protein expression that accompany the progression from normal ductal (ND) cell, to IPMN to PDAC may provide avenues for improved earlier detection. In this study, we present an optimized spatial tissue proteomics workflow, termed SP-Max (Spatial Proteomics Optimized for Maximum Sensitivity and Reproducibility in Minimal Sample), designed to maximize protein recovery and quantification from limited laser micro dissected (LMD) samples. Our workflow enabled the identification of more than 6,000 proteins and the quantification of over 5,200 protein groups from FFPE tissue contours of pancreatic tissues. Comparative analyses across ND, IPMN, and PDAC revealed critical molecular differences in protein pathways and potential markers of progression. SP-Max provides a systematic, reproducible approach that significantly enhances our ability to study precancerous lesions and cancer progression in pancreatic tissues at unprecedented resolution.

PMID:40654937 | PMC:PMC12247709 | DOI:10.1101/2025.05.01.651678

A 23-gene multi-omics signature predicts prognosis and treatment response in non-small cell lung cancer

Discov Oncol. 2025 Jul 23;16(1):1391. doi: 10.1007/s12672-025-03243-2.

ABSTRACT

We developed the first multi-omics prognostic signature integrating 19 programmed cell death (PCD) pathways and organelle functions (mitochondria, lysosomes, Golgi apparatus) to predict prognosis and immunotherapy response in non-small cell lung cancer (NSCLC). (2) Methods: By combining single-cell RNA-seq, bulk transcriptomics, and deep neural networks (DNN), we identified a 23-gene signature validated across four cohorts (AUC 0.696–0.812). Conducted MR analysis to explore causal links between signature genes and NSCLC incidence, providing biological insights. (3) Results: A prognostic signature was developed, including 23 prognostic genes related to 19 PCD patterns and three organelle functions. The signature demonstrated powerful performance in predicting NSCLC prognosis, immune in-filtration, and therapeutic response. Established DNN models showed high value in predicting risk score groupings of NSCLC. MR analysis for combined SNP information of the 23 prognostic genes suggested a link to the high incidence of NSCLC. Individual MR analysis showed that HIF1A and SQLE expression had a causal effect on NSCLC incidence. (4) Conclusion: This signature stratifies high-risk patients with immunosuppressive microenvironments and predicts enhanced sensitivity to gemcitabine and PD-1 inhibitors, offering a roadmap for personalized NSCLC management.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03243-2.

PMID:40699399 | PMC:PMC12287486 | DOI:10.1007/s12672-025-03243-2

Molecular characterization of breast cancer and multiple primary malignancies: the latest application using unmarked quantitative proteomics

Int J Surg. 2025 Jul 22. doi: 10.1097/JS9.0000000000002999. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer remains the most prevalent malignancy among women, and patients presenting with both breast and lung cancer pose significant challenges in clinical diagnosis and treatment. Currently, comprehensive multi-omics analyses for such multiple malignancies are lacking.

METHODS: An integrated multi-omics analysis was performed, incorporating quantitative proteomics and radiomics data from patients with single primary breast cancer as well as those with multiple primary tumors (breast and lung cancer).

RESULTS: Quantitative proteomics analysis revealed four distinct molecular signatures (Types I-IV). Patients with single breast cancer exhibited driving pathways primarily linked to cell proliferation (e.g., HER2), whereas those with multiple breast cancers showed enrichment in ER-related and proliferative pathways. In contrast, patients with multiple lung cancers displayed pathways associated with immune response and immune escape. Additionally, immune subtyping identified three distinct immune landscapes (Types I-III). Radiomic analysis demonstrated strong correlations between these molecular/immune subtypes and imaging findings. Patients with high imaging information scores exhibited pronounced tumor heterogeneity and reduced immune infiltration.

CONCLUSIONS: This study provides new insights into the molecular pathogenesis of multiple primary malignancies, particularly breast and lung cancer.

PMID:40694032 | DOI:10.1097/JS9.0000000000002999

Liquid Biopsy: Current advancements in clinical practice for bladder cancer

J Liq Biopsy. 2025 Jul 8;9:100310. doi: 10.1016/j.jlb.2025.100310. eCollection 2025 Sep.

ABSTRACT

Bladder cancer is the ninth most common malignancy worldwide, with two clinically distinct forms: non-muscle-invasive disease, characterized by high recurrence and excellent long-term survival, and muscle-invasive disease, associated with poorer outcomes. Current surveillance-cystoscopy and urine cytology-offers high specificity but is invasive, costly, and insensitive to low-grade tumors, underscoring the need for reliable, non-invasive biomarkers. Liquid biopsy approaches in urine and blood have demonstrated promise for real-time assessment of tumor burden, molecular heterogeneity, and early recurrence. Circulating tumor DNA (ctDNA) assays detect tumor-derived genetic and epigenetic alterations, enabling dynamic monitoring of minimal residual disease and treatment response. Methylation-based tests and CpG-targeted sequencing in urine achieve high diagnostic accuracy, potentially reducing dependence on cystoscopy. Molecular classification of bladder tumors into luminal and basal subtypes has refined therapeutic strategies: FGFR inhibitors for luminal-papillary tumors, EGFR-targeted and chemotherapy approaches for basal/squamous cases, and immune-checkpoint inhibitors guided by immune-infiltration profiles. Integration of artificial intelligence with multi-omic liquid biopsy data further enhances predictive modeling for recurrence, treatment response, and minimal residual disease detection. Despite these advances, clinical implementation faces challenges including pre-analytical variability, lack of standardized assays, limited prospective validation, and unclear cost-effectiveness. Harmonized protocols, large multicenter trials, and health-economic evaluations are essential to translate liquid biopsy technologies into routine practice. Future integration with advanced imaging, tissue biopsy, and digital pathology-supported by multidisciplinary collaboration and formal guideline endorsement-holds the potential to personalize bladder cancer management, reduce invasive procedures, and improve patient outcomes.

PMID:40698358 | PMC:PMC12281373 | DOI:10.1016/j.jlb.2025.100310

Integrated Multi-Omics Profiling Identifies PDZ-Binding Kinase (PBK) as a Novel Prognostic Biomarker in Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2025 Jul 17;12:1453-1469. doi: 10.2147/JHC.S493907. eCollection 2025.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) necessitates novel immunotherapeutic targets. PBK, a cancer/testis antigen (CTA), was identified as a pivotal hub gene influencing prognosis, tumor mutation burden (TMB), and immune microenvironment remodeling.

METHODS: PBK was prioritized using weighted gene co-expression network analysis (WGCNA) and differential expression screening in the TCGA-LIHC cohort, intersected with curated CTAs. Analyses assessed correlations with clinicopathological features (TNM stage, survival), genomic characterization (mutation frequencies), and functional validation via siRNA-mediated PBK knockdown in Huh7 cells (migration assay). Single-cell RNA sequencing (scRNA-seq) profiled of the tumor immune microenvironment.

RESULTS: PBK overexpression was significantly correlated with advanced TNM stage (P < 0.05) and poor survival (log-rank P = 0.003). Genomic analysis revealed distinct mutation profiles: high-PBK tumors exhibited increased TP53 mutation frequency (39% vs 17%) but decreased CTNNB1 mutations (20% vs 31%). Patients exhibiting with combined PBK overexpression and high TMB demonstrated the poorest prognosis. Functional validation confirmed that PBK knockdown significantly inhibited Huh7 cell migration capacity (P < 0.05). scRNA-seq analysis showed PBK-enriched tumors contained elevated proportions of immunosuppressive SPP1(+) macrophages (22.33% vs 6.6%, FDR corrected P < 0.001) and CD8(+) SLC4A10(+) MAIT cells (9.82% vs 4.7%, FDR corrected P < 0.001).

CONCLUSION: PBK synergistically drives HCC progression through three synergistic mechanisms: (1) promoting oncogenic mutation accumulation (eg, TP53), (2) increasing metastatic potential, and (3) reprogramming an immune-suppressive microenvironment enriched for SPP1(+) macrophages and CD8(+)SLC4A10(+) MAIT cells. This establishes PBK as a dual-purpose biomarker for prognostic stratification and immunotherapy resistance prediction, providing a mechanistic rationale for developing PBK-targeted therapies in HCC.

PMID:40697330 | PMC:PMC12279550 | DOI:10.2147/JHC.S493907

Nanobody therapy rescues behavioural deficits of NMDA receptor hypofunction

Nature, Published online: 23 July 2025; doi:10.1038/s41586-025-09265-8

A bivalent biparatopic nanobody penetrates the brain, binds to and potentiates the activity of homodimeric metabotropic glutamate receptor 2, correcting cognitive deficits in two preclinical mouse models with endophenotypes resulting from NMDA receptor hypofunction.

Complex genetic variation in nearly complete human genomes

Nature, Published online: 23 July 2025; doi:10.1038/s41586-025-09140-6

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

Multiomics Analysis Reveals Insights into Potential Drivers of Pancreatic Islet Pathology in Type 2 Diabetes

ACS Omega. 2025 Jun 30;10(27):28782-28796. doi: 10.1021/acsomega.4c10637. eCollection 2025 Jul 15.

ABSTRACT

Despite the high prevalence of type 2 diabetes (T2D), the mechanisms driving pathology in pancreatic islet β cells remain poorly understood. We utilized a multiomics approach to evaluate the transcriptional and biochemical makeup of islets from human organ donors with T2D and nondiabetic controls. Transcriptomic (N = 10), proteomic (N = 6), and untargeted high-resolution metabolomic (N = 10) data were analyzed individually and then integrated using sparse partial least-squares regression, and differential network analysis was performed. In individual data sets, 25 transcripts, 30 proteins, and 30 metabolites were differentially abundant between T2D and nondiabetic islets, representing some pathways not previously characterized in T2D islets including purine and pyrimidine, branched-chain amino acid, and histidine metabolism. Network analysis of integrated data sets highlighted disrupted relationships among features in T2D islets compared to those from nondiabetic individuals. Fatty and amino acid metabolism and immune activity were identified as prominent drivers of the distinctions in biochemical interactions in T2D networks. Our findings also suggested greater abundance and influence of industrial chemicals, including polychlorinated and polybrominated biphenyls, in T2D islets. This pilot study demonstrates that multiomics profiling can identify candidate molecules and mechanisms impacting islet cell activity in T2D, which could represent targets for therapeutic intervention.

PMID:40687044 | PMC:PMC12268419 | DOI:10.1021/acsomega.4c10637

Actin-Like Protein 6A as an Oncogene and Therapeutic Target in Cancer

Int J Med Sci. 2025 Jun 12;22(12):2906-2918. doi: 10.7150/ijms.113736. eCollection 2025.

ABSTRACT

ACTL6A, a core subunit of the SWI/SNF chromatin remodeling complex, has emerged as a critical oncogenic driver across multiple malignancies. Recent studies reveal that aberrant ACTL6A overexpression promotes tumor initiation, progression, and metastasis by orchestrating chromatin remodeling, transcriptional reprogramming, and crosstalk with key signaling pathways (e.g., Hippo/YAP, Notch, and PI3K/AKT). This review systematically synthesizes evidence from in vitro, in vivo, and clinical studies spanning hepatocellular carcinoma, breast cancer, glioblastoma, and 10 other cancer types, highlighting ACTL6A's dual role as a chromatin remodeler and an independent oncogenic effector. Key mechanisms include sustaining cancer stemness, suppressing apoptosis, enhancing DNA repair, and driving metabolic reprogramming. Clinically, ACTL6A overexpression correlates with advanced tumor stage, therapy resistance, and poor prognosis, positioning it as a promising prognostic biomarker and therapeutic target. We further discuss emerging strategies to inhibit ACTL6A (e.g., siRNA, small-molecule inhibitors) and propose combinatorial approaches to overcome drug resistance. By integrating multi-omics data and preclinical models, this review not only clarifies ACTL6A's context-dependent oncogenic networks but also bridges mechanistic insights to translational challenges, offering a roadmap for future research and therapeutic development.

PMID:40657395 | PMC:PMC12243864 | DOI:10.7150/ijms.113736

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets

MedComm (2020). 2025 Jul 11;6(7):e70292. doi: 10.1002/mco2.70292. eCollection 2025 Jul.

ABSTRACT

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinical translation. This review systematically categorizes CAF subtypes by origin, biomarkers, and TME-specific functions, focusing on their roles in chemoresistance, maintenance of stemness, and formation of immunosuppressive niches. We evaluate emerging targeting approaches, including selective depletion of tumor-promoting subsets (e.g., fibroblast activation protein+ CAFs), epigenetic reprogramming toward antitumor phenotypes, and inhibition of CXCL12/CXCR4 or transforming growth factor-beta signaling pathways. Spatial multiomics-driven combinatorial therapies, such as the synergistic use of CAFs and immune checkpoint inhibitors, are highlighted as strategies to overcome microenvironment-driven resistance. By integrating CAF biology with translational advances, this work provides a roadmap for developing subtype-specific biomarkers and precision stromal therapies, directly informing efforts to disrupt tumor-stroma coevolution. Key concepts include spatial transcriptomics, stromal reprogramming, and tumor-stroma coevolution, offering actionable insights for both mechanistic research and clinical innovation.

PMID:40656546 | PMC:PMC12246558 | DOI:10.1002/mco2.70292

  • ✇MRD
  • Circulating tumor DNA in B cell lymphomas Marco Fangazio · Laurent Dewispelaere
    Curr Opin Oncol. 2025 Sep 1;37(5):408-413. doi: 10.1097/CCO.0000000000001178. Epub 2025 Jul 2.ABSTRACTPURPOSE OF REVIEW: This review evaluates the importance of circulating tumor DNA (ctDNA) as a minimally invasive tool in lymphoma management.RECENT FINDINGS: Current literature demonstrates ctDNA's ability to alleviate the shortcomings of standard biopsy and imaging, providing real-time insights into tumor burden, clonal evolution, and treatment resistance. In Hodgkin lymphoma, ctDNA allows for
     

Circulating tumor DNA in B cell lymphomas

14 July 2025 at 18:00

Curr Opin Oncol. 2025 Sep 1;37(5):408-413. doi: 10.1097/CCO.0000000000001178. Epub 2025 Jul 2.

ABSTRACT

PURPOSE OF REVIEW: This review evaluates the importance of circulating tumor DNA (ctDNA) as a minimally invasive tool in lymphoma management.

RECENT FINDINGS: Current literature demonstrates ctDNA's ability to alleviate the shortcomings of standard biopsy and imaging, providing real-time insights into tumor burden, clonal evolution, and treatment resistance. In Hodgkin lymphoma, ctDNA allows for comprehensive genomic profiling and treatment monitoring. In diffuse large B-cell lymphoma (DLBCL), ctDNA correlates with disease burden and is valuable for tracking resistance, especially in CAR T-cell therapy. In rare subtypes like primary central nervous system lymphoma (PCNSL) and intravascular large B-cell lymphoma (IVLBCL), ctDNA enhances diagnostic precision and enables early relapse detection. Even in indolent lymphomas, ctDNA could prove useful in relapse monitoring and risk assessment.

SUMMARY: CtDNA analysis could become a key element in personalized lymphoma management, enabling earlier interventions and tailored treatment strategies. However, future efforts should focus on harmonizing methodologies and validating findings in large-scale trials to allow these techniques to be adopted in routine practice.

PMID:40658005 | DOI:10.1097/CCO.0000000000001178

A clinical road map for single-cell omics

Despite initial forays into clinical settings, single-cell technologies do not yet routinely inform medical decision-making. Here, we identify and categorize barriers hindering the clinical deployment of single-cell omics. We articulate a framework to identify patient subpopulations that stand to benefit from such biomarkers and outline the requirements to derive actionable clinical readouts.

The generative era of medical AI

10 July 2025 at 08:00
Significant progress has been made in recent years in applying large language models and multimodal artificial intelligence to health and medicine, transforming diagnostics, patient interactions, and medical forecasting, although challenges like privacy, regulation, and system integration remain before widespread clinical adoption.

Clinical performance evaluation of a plasma dual-target methylation test for the detection of primary liver cancer: a multicenter study

Primary liver cancer (PLC) is a global health concern. The plasma dual-target methylation (PDTM) test, which interrogates the methylation status of GNB4 and Riplet, exhibits a commendable ability to discriminate ...
  • ✇MIT Technology Review
  • Building an innovation ecosystem for the next century MIT Technology Review Insights
    Michigan may be best known as the birthplace of the American auto industry, but its innovation legacy runs far deeper, and its future is poised to be even broader. From creating the world’s largest airport factory during World War II at Willow Run to establishing the first successful polio vaccine trials in Ann Arbor to the invention of the snowboard in Muskegon, Michigan has a long history of turning innovation into lasting impact.  Now, with the creation of a new role, chief innovation
     

Building an innovation ecosystem for the next century

Michigan may be best known as the birthplace of the American auto industry, but its innovation legacy runs far deeper, and its future is poised to be even broader. From creating the world’s largest airport factory during World War II at Willow Run to establishing the first successful polio vaccine trials in Ann Arbor to the invention of the snowboard in Muskegon, Michigan has a long history of turning innovation into lasting impact. 

Now, with the creation of a new role, chief innovation ecosystem officer, at the Michigan Economic Development Corporation (MEDC), the state is doubling down on its ambition to become a modern engine of innovation, one that is both rooted in its industrial past and designed for the evolving demands of the 21st century economy.  

“How do you knit together risk capital founders, businesses, universities, and state government, all of the key stakeholders that need to be at the table together to build a more effective innovation ecosystem?” asks Ben Marchionna, the first to hold this groundbreaking new position. 

Leaning on his background in hard tech startups and national security, Marchionna aims to bring a “builder’s thinking” to the state government. “I’m sort of wired for that—rapid prototyping, iterating, scaling, and driving that muscle into the state government ecosystem,” he explains.

But these efforts aren’t about creating a copycat Silicon Valley. Michigan’s approach is uniquely its own. “We want to develop the thing that makes the most sense for the ingredients that Michigan can bring to bear to this challenge,” says Marchionna. 

This includes cultivating both mom-and-pop businesses and tech unicorns, while tapping into the state’s talent, research, and manufacturing DNA. 

In an era where economic development often feels siloed, partisan, and reactive, Michigan is experimenting with a model centered on long-term value and community-oriented innovation. “You can lead by example in a lot of these ways, and that flywheel really can get going in a beautiful way when you step out of the prescriptive innovation culture mindset,” says Marchionna.

This episode of Business Lab is produced in partnership with the Michigan Economic Development Corporation.

Full Transcript 

Megan Tatum: From MIT Technology Review. I’m Megan Tatum, and this is Business Lab, the show that helps business leaders make sense of new technologies coming out of the lab and into the marketplace. 

Today’s episode is brought to you in partnership with the Michigan Economic Development Corporation. 

Our topic today is building a statewide innovation economy. Now, the U.S. state of Michigan has long been recognized as a leader in vehicle and mobility innovation. Detroit put it on the map, but did you know it’s also the birthplace of the snowboard or that the University of Michigan filed more than 600 invention disclosures in 2024, second only to the Massachusetts Institute of Technology, or that in the past five years, 40% of the largest global IPOs have been Michigan built companies?

Two words for you: innovation ecosystem. 

My guest is Ben Marchionna, chief innovation ecosystem officer at the Michigan Economic Development Corporation, the MEDC. 

Ben, thank you ever so much for joining us.

Ben Marchionna: Thanks, Megan. Really pleased to be here.

Megan: Fantastic. And just to set some context to get us started, I wondered if we could take a kind of high-level look at the economic development landscape. I mean, you joined the MEDC team last year as Michigan’s first chief innovation ecosystem officer. In fact, you were the first to hold such a role in the country, I believe. I wondered if you could talk a bit about your unique mission and how this economic development approach differs from efforts in other states.

Ben: Yeah, sure would love to. Probably worth pointing out that while I’ve been in this role for about a year now, it was indeed a first-of-its-kind role in the state of Michigan and first of its kind in the country. The slight difference in the terminology, chief innovation ecosystem officer, it differs a little bit from what folks might think of as a chief innovation officer. I’m not all that focused on driving innovation within government, which is what some other chief innovation officers would be focused on around the country. Instead, you can think of my role as Michigan’s chief architect for innovation, if you will. So, how do you knit together risk capital founders, businesses, universities, and state government, all of the key stakeholders that need to be at the table together to build a more effective innovation ecosystem? I talk a lot about building connective tissues that can achieve one plus one equals three outcomes.

Michigan’s got all kinds of really interesting ingredients and has the foundation to take advantage of the moment in a really interesting way over the next decades as we look to supercharge some of the growth of our innovation ecosystem development.

My charter is relatively simple. It’s to help make sure that Michigan wins in a now hyper-competitive global economy. And to do that, I end up being super focused on orienting us towards a growth and innovation-driven economy. That can mean a lot of different things, but I ultimately came to the MEDC and the role within the state with a builder’s mindset. My background is not in traditional economic development, it’s in not government at all. I spent the last 10 years building hard tech startups, one in Ann Arbor, Michigan, and another one in the Northern Virginia area. Before that, I spent a number of years at, think of it like, an innovation factory at Lockheed Martin Skunk Works in the Mojave Desert, working on national security projects.

I’m sort of wired for that, builder’s thinking, rapid prototyping, iterating, scaling, and driving that muscle into the state government ecosystem. I think it’s important that the government also figure out how to pull out all the stops and be able to move at the speed that founders expect. A bias towards action, if you will. And so this is ultimately what my mission is. There are a lot of real interesting things that the state of Michigan can bring to bear to building our innovation ecosystem. And I think, tackling it with this sort of a mindset, I am absolutely optimistic for the future that we’ve got ahead of us.

Megan: Fantastic. It almost sounds like your role is sort of building a statewide startup incubator of sorts. As we mentioned in the opening, Michigan actually has a really interesting innovation history even in addition to the advances in the automotive industry. I wondered if you could talk a bit more about that history and why Michigan, in particular, is poised to support that sort of statewide startup ecosystem.

Ben: Yeah, absolutely. And I would even broaden it. Building the startup ecosystem is one of the essential layers, but to be able to successfully do that, we have to bring in the research universities, we have to bring in the corporate innovation ecosystem, we have to bring in the risk capital, et cetera. So yes, absolutely, startups are important. And equally as important are all of these other elements that are necessary for a startup ecosystem to thrive, but are also the levers that are just sitting there waiting for us to pull them.

And we can get into some of the details over the course of our chat today on the auto industry and how this fits into it, but Michigan does a lot more than just automotive stuff. And you noted, I think, the surfboard as an example in the intro. Absolutely correct. We have a reputation as Motor City, but Michigan’s innovation record is a lot weirder in a fun way and richer than just cars.

Early 20th century, mostly industrial moonshot innovation. So first paved mile of concrete was in Detroit in 1909. A few years later, this is when the auto sector started to really come about with Henry Ford’s moving assembly line. Everyone tends to know about those details. But during World War II, Willow Run Airport sort of smack between Detroit and Ann Arbor, Michigan they had the biggest airplane factory in the world. They were cranking out B-24 bombers once every 63 minutes, and I’ve actually been to the office that Henry Ford and Charles Lindbergh shared. It’s still at the airport. And it was pretty cool because Henry Ford had a window built into the office that looked sort of around the corner so that he could tick off as airplanes rolled out of the hanger and make sure that they were following the same high rate production mentality that the auto sector was able to develop over the decades prior. 

And so they came in to help make sure that you could leverage that industrial sector to drive very rapid production, the at-scale mentality, which is also a really important part of the notion of re-industrialization that is taking hold across the country now. Happy to get into that a bit, but yeah, Willow Run, I don’t think most folks realize that that was the biggest airplane factory in the world sitting right here in Michigan.

And all of this provided the mass production DNA that was able to help build the statewide supplier base. And today, yes, we use that for automotive, EVs, space hardware, batteries, you name it. But this is the foundation, I think, that we’ve got to be able to build on in the future. In the few decades since you saw innovations in sports, space, advanced materials, it’s like the sixties to the eighties. You said the snowboard. That was invented in Muskegon on the west side of the state in 1965.

Dow Chemical’s here in a really big way. They’ve pioneered silicone and advanced plastics in Michigan. University of Michigan’s Dr. Thomas Francis is the world’s first successful polio vaccine trials that were pioneered out of Ann Arbor, and that Big 10 research horsepower that we’ve got in the state, between the University of Michigan, Michigan State University. We also have Wayne State University in Detroit, which is a powerhouse. And then Michigan Tech University in the Upper Peninsula just recently became an R1 research institution, which essentially means those top-tier research powerhouses and that culture of tinkering matter a lot today.

I think in more recent history, you saw design and digital innovations emerge. I don’t think a lot of people appreciate that Herman Miller and Steelcase reinvented office ergonomics on the west side of the state, or that Stryker is based in Kalamazoo. They became a global medical device powerhouse over the last couple of decades, too. Michigan’s first unicorn, Duo Security, the two-factor authentication among many other things that they do there, was sold to Cisco in 2018 for 2.35 billion.

Like I said, the first unicorn in the few years since we’ve had another 10 unicorns. And I think probably what would be surprising to a lot of people is it’s in sectors well beyond mobility, it’s marketplace like StockX, FinTech, logistics, cybersecurity, of course. It’s a little bit of everything, and I think that goes to show that some of the fabric that exists within Michigan is a lot richer than what people think of, Motor City. We can scale software, we can scale life sciences innovation. It’s not just metal bending, and I talked about re-industrialization earlier. So I think about where we are today, there’s a hard tech renaissance and a broad portfolio of other high-growth sectors that Michigan’s poised to do really well in, leveraging all of that industrial base that has been around for the last century. I’m just super excited about the future and where we can take things from here.

Megan: I mean, genuinely, a really rich and diverse history of innovation that you’ve described there.

Ben: That’s right.

Megan: And last year, when Michigan’s Governor Whitmer announced this new initiative and your position, she noted the need to foster this sort of culture of innovation. And we hear that a lot that terminal in the context of company cultures. It’s interesting to hear in the context of a U.S. state’s economy. I wonder what your strategy is for building out this ecosystem, and how do you foster a state’s innovation culture?

Ben: Yeah, it’s an awesome point, and I think I mentioned earlier that I came into the role with this builder’s mentality. For me, this is how I am wired to think. This is how a lot of the companies and other founders that I spent a lot of time with, this is how they think. And so bringing this to the state government, I think of Blue Origin, Jeff Bezos’ space company, their motto, the English translation at least of it, is “Step by Step, Ferociously.” And I think about that as a lot as a proxy for how I do that within the state government. There’s a lot of iterative work that needs to happen, a lot of coaching and storytelling that happens to help folks understand how to think with that builder’s mindset. The wonderful news is that when you start having that conversation, this is one of those in these complicated political times, this is a pretty bipartisan thing, right?

The notion of how to build small businesses that create thriving main street communities while also supporting high-growth, high-tech startups that can drive prosperity for all, and population growth, while also being able to cover corporate innovation and technology transfer out of universities. All of these things touch every corner of the state.

And Michigan’s a surprisingly large and very geographically diverse state. Most of the things that we tend to be known for outside the state are in a pretty small corner of Southeast Michigan. That’s the Motor City part, but we do a lot and we have a lot of really interesting hubs for innovation and hubs for entrepreneurship, like I said, from the small mom-and-pop manufacturing shop or interest in clothing business all the way through to these insane life sciences innovations being spun out of the university. Being able to drive this culture of innovation ends up being applicable really across the board, and it just gets people really fired up when you start talking about this, fired up in a good way, which is, I think, what’s really fantastic.

There’s this notion of accelerating the talent flywheel and making sure that the state can invest in the cultivation of really rich communities and connections, and this founder culture. That stuff happens organically, generally, and when you talk about building startup ecosystems, it’s not like the state shows up and says, “Now you’re going to be more innovative and that works.” That is not the case.

And so to be able to develop those things, it’s much more about this notion of ecosystem building and getting the ingredients and puzzle pieces in the right place, applying a little bit of funding here and there, or loosening a restriction here or there, and then letting the founders do what they do best, which is build. And so this is what I think I end up being super passionate about within the state. You can lead by example in a lot of these ways, and that flywheel that I mentioned really can get going in a beautiful way when you step out of the prescriptive innovation culture mindset.

Megan: And given that role, I wonder what milestones the campaign has experienced in your first year? Could you share some highlights and some developing projects that you’re really excited about?

Ben: We had a recent one, I think that was pretty tremendous. Just a couple of months ago, Governor Whitmer signed into law a bipartisan legislation called the Michigan Innovation Fund. This was a multi-year effort that resulted in the state’s biggest investment in the innovation ecosystem development in over two decades. A lot of this funding is going to early stage venture capital firms that will be able to support the broad seeding of new companies and ideas, keep talent within the state from some of those top tier research institutions, bring in really high quality companies that early stage, growth stage companies from out of state, and then develop or supercharge some of that innovation ecosystem fabric that ties those things together. So that connective tissue that I talked about, and that was an incredible win to launch the year with.

This was just back in January, and now we’re working to get some of those funds out over the course of the next month or two so we can put them to use. What was really interesting about that was, it wasn’t just a top-down thing. This was supported from the top all the way up to and including Governor Whitmer. I mentioned bipartisan support within Michigan’s legislature and then bottom-up from all of the ecosystem partners, the founders, the investors advocating as a whole block, which I think is really powerful. Rather than trying to go for one-off things, this huge coalition of the willing got together organically and advocated for, hey, this is why this is such a great moment. This is the time to invest. And Governor Whitmer and the legislators, they heard that call, and we got something done, and so that happened relatively quickly. Like I said, biggest investment in the last two decades, and I think we’re poised to have some really great successes in the coming year as well.

Another really interesting one that I haven’t seen other states do yet, Governor Whitmer, around a year ago, signed an executive order called the Infrastructure for Innovation. Essentially, what that does is it opens up state department and agency assets to startups in the name of moving the ball forward on innovation projects. And so if you’re a startup and you need access to some very hard-to-find, very expensive, maybe like a test facility, you can use something that the state has, and all of the processes to get that done are streamlined so that you’re not beating your head against a wall. Similarly, the universities and even federal labs and corporate resources, while an executive order can’t compel those folks to do that, we’ve been finding tremendous buy-in from those stakeholders who want to volunteer access to their resources.

That does a lot of really good things, certainly for the founders, that provides them the launchpad that they need. But for those corporations and universities, and whatnot, a lot of them have these very expensive assets sitting around wildly underutilized, and they would be happy to have people come in and use them. That also gives them exposure to some of the bleeding-edge technology that a lot of these startups today are developing. I thought that was a really cool example of state government leadership using some of the tools that are available to a governor to get things moving. We’ve had a lot of early wins with startups here that have been able to leverage what that executive order was able to do for them.

Here we are talking about the MIT Technology Review to tie in an MIT piece here, we also started a Team Michigan for MIT’s REAP program. It’s the Regional Entrepreneurship Acceleration Program, and this is one of the global thought leaders on best practices for innovation ecosystem development. And so we’ve got a cohort of about a dozen key leaders from across all of those different stakeholders who need to have a seat at the table for this ecosystem development.

We go out to Cambridge twice a year for a multi-day workshop, and we get to talk about what we’ve learned as best practices, and then also learn from other cohorts from around the world on what they’ve done that is great. And then also get to hear some of the academic best practices that the MIT faculty have discovered as part of this area of expertise. And so that’s been a very interesting way for us to be able to connect outside of the state government boundaries, if you will. You sort of get out there and see where the leading edge is and then come back and be able to talk about the things that we learned from all of these other global cohorts. So always important to be focused on best practices when you’re trying to do new things, especially in government.

Megan: Sounds like there are some really fantastic initiatives going on. It sounds like a very busy first year.

Ben: It’s been a very busy first year couldn’t be more thrilled about it.

Megan: Fantastic. And in early 2023, I know that Newlab partnered with Michigan Central to establish a startup incubator too, which brought in more than a hundred startups just in its first 14 months. I wonder if you could talk a bit about how the incubator fits in with the statewide startup ecosystem and the importance of partnerships, too, for innovation.

Ben: Yeah, a key element, and I think the partnerships piece is essential here. Newlab is one of the larger components of the Southeast Michigan and especially the Detroit innovation ecosystem development. They will hit their two-year launch anniversary in just a couple of weeks, here I think. This will be mid-May, it will be two years and in that time, they’ve now got 140 plus startups all working out of their space, and Newlab they’re actually headquartered in Brooklyn, New York, but they run this big startup accelerator incubator out of Detroit as well and so this is sort of their second flagship location. They’ve been a phenomenal partner, and so speaking of the partnerships, what do those do?

They de-risk the technologies to help enable broader adoptions. Corporations can provide early revenues, the state can provide non-dilutive grant matching. Universities can bring IP and this renewable source of talent generation, and being able to stitch together all of those pieces can create some really interesting unlocks for startups to grow. But again, also this broader entrepreneurship and innovation ecosystem to really be able to thrive.

Newlab has been thrilled with their partnership in Southeast Michigan, and I think it’s a model that can be tailored across the state so that, depending on what assets are available in your backyard, you can make sure that you can best harness those for future growth.

Megan: Fantastic. What’s the long-term vision for the state’s innovation landscape when you think about it in five, 10 years from now? What do you envisage?

Ben: Amazing question. This is probably what I get most excited about. I think earlier we talked about the Willow Run B-24 bomber plant. That is what made Michigan known as the arsenal of democracy back in the day. I want Michigan to be the arsenal of innovation. We’re not trying to recreate a Silicon Valley. Silicon Valley does certain things, not trying to recreate what El Segundo wants to do in hard tech or New York City in FinTech, and all of these other things. We want to develop the thing that makes the most sense for the ingredients that Michigan can bring to bear to this challenge.

I think that becoming the Midwest arsenal of innovation, that’s something that Michigan is very well poised to use as a springboard for the decades to come. I want us to be the default launch pad for building a hard tech company, a life sciences company, an agricultural tech company. You name it. If you’ve got a design prototype and want to mass produce something, don’t want to hop coast, you want to be somewhere that has a tremendous quality of life, an affordable place, somewhere that government is at the table and willing to move fast, this is a place to do that.

That can be difficult to do in some of the more established ecosystems, especially post-covid, as a lot of them are going through really big transition periods. Michigan’s already a top 10 state for business in the next 10 years. I want us to be a top 10 state for employment, top 10 state for household median income for post-secondary education attainment, and net talent migration. Those are my four top tens that I want to see in the next 10 years. And we covered a lot of topics today, but I think those are the reasons that I am super optimistic about being able to accomplish those.

Megan: Fantastic. Well, I’m tempted to move to Michigan, so I’m sure plenty of other people will be now, too. Thank you so much, Ben. That was really fascinating.

Ben: Thanks, Megan. Really delighted to be here.

Megan: That was Ben Marchionna, chief innovation ecosystem officer at the Michigan Economic Development Corporation, whom I spoke with from Brighton, England. 

That’s it for this episode of Business Lab. I’m your host, Megan Tatum. I’m a contributing editor and host for Insights, the custom publishing division of MIT Technology Review. We were founded in 1899 at the Massachusetts Institute of Technology, and you can find us in print on the web and at events each year around the world. For more information about us and the show, please check out our website at technologyreview.com.

This show is available wherever you get your podcasts, and if you enjoy this episode, we hope you’ll take a moment to rate and review us. Business Lab is a production of MIT Technology Review. This episode was produced by Giro Studios. Thanks ever so much for listening.

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